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1.
J Dent Sci ; 17(1): 145-154, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35028032

RESUMO

Background/purpose: Autophagy is involved in controlling differentiation of various cell types. The present study aimed to investigate the mechanism related to autophagy in regulating odontogenic differentiation of dental pulp cells. Materials and methods: Human dental pulp cells (HDPCs) were cultured in differentiation inductive medium (DM) and odontoblastic differentiation and mineralization were evaluated by alkaline phosphatase (ALP) staining and Alizarin red S staining, respectively. Tooth cavity preparation was made on the mesial surface of lower first molars in rat. The expression of autophagy-related signal molecules was detected using Western blot analysis and Immunohistochemistry. Results: HDPCs cultured in DM showed increased autophagic flux and declined phosphorylation of phosphoinositide 3-kinases (PI3K), protein kinase B (Akt), and mTOR. Dentin matrix protein-1 (DMP-1) and dentin sialoprotein (DSP), markers of odontoblastic differentiation, were upregulated and autophagic activation showing increased LC3-II and decreased p62 levels was observed during odontogenic differentiation of HDPCs. However, PI3K blocker 3-methyladenine (3MA), lentiviral shLC3 and Akt activator SC79 attenuated the expression of LC3II as well as DMP-1, ALP activity and mineralization enhanced in HDPCs under DM condition. In addition, 3MA, shLC3 and SC79 recovered the expression of pluripotency factor CD146, Oct4 and Nanog downregulated in DM condition. In rat tooth cavity preparation model, the expression of LC3B and DMP-1 was elevated near odontoblast-dentin layer during reparative dentin formation, whereas 3MA significantly reduced the expression of LC3B and DMP-1. Conclusion: These findings indicated autophagy promotes the odontogenic differentiation of dental pulp cells modulating stemness via PI3K/Akt inactivation and the repair of pulp.

2.
Shock ; 57(2): 168-174, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35025842

RESUMO

BACKGROUND: Disseminated intravascular coagulation (DIC) is a life-threatening complication of septic shock; however, risk factors for its development after admission are unknown. Thromboelastography (TEG) can reflect coagulation disturbances in early non-overt DIC that are not detected by standard coagulation tests. This study investigated the risk factors including TEG findings as early predictors for DIC development after admission in septic shock patients with non-overt DIC. METHODS: This retrospective observation study included 295 consecutive septic shock patients with non-overt DIC at admission between January 2016 and December 2019. DIC was defined as an International Society on Thrombosis and Hemostasis (ISTH) score ≥ 5. The primary outcome was non-overt DIC at admission that met the ISTH DIC criteria within 3 days after admission. RESULTS: Of the 295 patients with non-overt DIC, 89 (30.2%) developed DIC after admission. The DIC group showed a higher ISTH score and 28-day mortality rate than the non-DIC group (2 vs. 3, P < 0.001; 13.6% vs. 27.0%, P = 0.008, respectively). The DIC rate increased with the ISTH score (7.7%, 13.3%, 15.8%, 36.5%, and 61.4% for scores of 0, 1, 2, 3, and 4, respectively). Among TEG values, the maximum amplitude (MA) was higher in the non-DIC group (P < 0.001). On multivariate analysis, an MA < 64 mm was independently associated with DIC development (odds ratio, 2.311; 95% confidence interval, 1.298-4.115). CONCLUSIONS: DIC more often developed among those with admission ISTH scores ≥ 3 and was associated with higher mortality rates. An MA < 64 mm was independently associated with DIC development in septic shock patients.

3.
Sci Rep ; 12(1): 767, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031675

RESUMO

Prism Adaptation (PA) is used to alleviate spatial neglect. We combined immersive virtual reality with a depth-sensing camera to develop virtual prism adaptation therapy (VPAT), which block external visual cues and easily quantify and monitor errors than conventional PA. We conducted a feasibility study to investigate whether VPAT can induce behavioral adaptations by measuring after-effect and identifying which cortical areas were most significantly activated during VPAT using functional near-infrared spectroscopy (fNIRS). Fourteen healthy subjects participated in this study. The experiment consisted of four sequential phases (pre-VPAT, VPAT-10°, VPAT-20°, and post-VPAT). To compare the most significantly activated cortical areas during pointing in different phases against pointing during the pre-VPAT phase, we analyzed changes in oxyhemoglobin concentration using fNIRS during pointing. The pointing errors of the virtual hand deviated to the right-side during early pointing blocks in the VPAT-10° and VPAT-20° phases. There was a left-side deviation of the real hand to the target in the post-VPAT phase, demonstrating after-effect. The most significantly activated channels during pointing tasks were located in the right hemisphere, and possible corresponding cortical areas included the dorsolateral prefrontal cortex and frontal eye field. In conclusion, VPAT may induce behavioral adaptation with modulation of the dorsal attentional network.

4.
Biochem Biophys Rep ; 29: 101190, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34988296

RESUMO

Particulate matter (PM) causes several diseases, including cardiovascular diseases (CVDs). Previous studies compared the gene expression patterns in airway epithelial cells and keratinocytes exposed to PM. However, analysis of differentially expressed gene (DEGs) in endothelial cells exposed to PM2.5 (diameter less than 2.5 µm) from fossil fuel combustion has been limited. Here, we exposed human umbilical vein endothelial cells (HUVECs) to PM2.5 from combustion of gasoline, performed RNA-seq analysis, and identified DEGs. Exposure to the IC50 concentrations of gasoline engine exhaust PM2.5 (GPM) for 24 h yielded 1081 (up-regulation: 446, down-regulation: 635) DEGs. The most highly up-regulated gene is NGFR followed by ADM2 and NUPR1. The most highly down-regulated gene is TNFSF10 followed by GDF3 and EDN1. Gene Ontology enrichment analysis revealed that GPM regulated genes involved in cardiovascular system development, tube development and circulatory system development. Kyoto Encyclopedia of Genes and Genomes and Reactome pathway analyses showed that genes related to cytokine-cytokine receptor interactions and cytokine signaling in the immune system were significantly affected by GPM. We confirmed the RNA-seq data of some highly altered genes by qRT-PCR and showed the induction of NGFR, ADM2 and IL-11 at a protein level, indicating that the observed gene expression patterns were reliable. Given the adverse effects of PM2.5 on CVDs, our findings provide new insight into the importance of several DEGs and pathways in GPM-induced CVDs.

5.
J Neurosci ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34987109

RESUMO

Astrocytes are critical for the development and function of synapses. There are notable species differences between human astrocytes and commonly used animal models. Yet, it is unclear whether astrocytic genes involved in synaptic function are stable or exhibit dynamic changes associated with disease states and age in humans, which is a barrier in understanding human astrocyte biology and its potential involvement in neurological diseases. To better understand the properties of human astrocytes, we acutely purified astrocytes from the cerebral cortices of over 40 humans across various ages, sexes, and disease states. We performed RNA sequencing to generate transcriptomic profiles of these astrocytes and identified genes associated with these biological variables. We found that human astrocytes in tumor-surrounding regions downregulate genes involved in synaptic function and sensing of signals in the microenvironment, suggesting involvement of peri-tumor astrocytes in tumor-associated neural circuit dysfunction. In aging, we also found downregulation of synaptic regulators and upregulation of markers of cytokine signaling, while in maturation we identified changes in ionic transport with implications for calcium signaling. In addition, we identified subtle sexual dimorphism in human cortical astrocytes, which has implications for observed sex differences across many neurological disorders. Overall, genes involved in synaptic function exhibit dynamic changes in the peritumor microenvironment and aging. This data provides powerful new insights into human astrocyte biology in several biologically relevant states, that will aid in generating novel testable hypotheses about homeostatic and reactive astrocytes in humans.SIGNIFICANCE STATEMENTAstrocytes are an abundant class of cells playing integral roles at synapses. Astrocyte dysfunction is implicated in a variety of human neurological diseases. Yet our knowledge of astrocytes is largely based on mouse studies. Direct knowledge of human astrocyte biology remains limited. Here, we present transcriptomic profiles of human cortical astrocytes, and we identified molecular differences associated with age, sex, and disease state. We found that peritumor and aging astrocytes downregulate genes involved in astrocyte-synapse interactions. These data provide necessary insight into human astrocyte biology that will improve our understanding of human disease.

6.
Adv Sci (Weinh) ; : e2101935, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34989173

RESUMO

There has been a significant clinical demand for lymph-directed anti-metastatic therapy as tumor-draining lymph nodes play pivotal roles in cancer metastasis which accounts for more than 90% of tumor-related deaths. Despite the high potential of nitric oxide (NO) in anti-cancer therapy owing to its biocompatibility and tumor cell-specific cytotoxicity, the poor stability and lack of target specificity of present NO donors and delivery systems have limited its clinical applications. Herein, a redox-triggered self-immolative NO prodrug that can be readily conjugated to various materials containing free thiol groups such as albumin, is reported. The prodrug and its conjugates demonstrate smart release of NO donor via intramolecular cyclization under reductive conditions, followed by spontaneously generating NO in physiological conditions. The albumin-prodrug conjugate inhibits tumor metastasis by inducing cytotoxicity preferentially on tumor cells after efficiently draining into lymph nodes. This novel prodrug can contribute to the development of on-demand NO delivery systems for anti-metastatic therapy and other treatments.

7.
Korean J Ophthalmol ; 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35067022

RESUMO

Purpose: This study evaluated the prognosis of patients with traumatic unilateral superior oblique palsy (SOP) and clinical factors associated with spontaneous resolution. Methods: Medical records of patients with traumatic unilateral SOP who visited two hospitals (*** and *** Hospital) between January 2015 and June 2020 were reviewed retrospectively. When traumatic unilateral SOP did not recover within at least 1 year of follow-up, no spontaneous resolution was considered. Both traumatic and ocular factors were evaluated to evaluate their association with spontaneous recovery. Results: Fifty-nine patients (mean age: 52.6 years, 48 men) were enrolled in this study. The mean interval from trauma to initial presentation was 3.9 months. The mean vertical deviation at initial presentation was 6.34 ± 5.22 (range: 0-25) PD. During the mean 24.1-month follow-up period, 28 (47.5%) patients achieved spontaneous resolution of SOP. Thirteen patients underwent surgical treatment for SOP. Vertical deviation <6 PD at the initial visit and low fundus torsion in the non-paretic eye and both eyes were significantly associated with spontaneous recovery (p < 0.05, logistic regression analysis). Traumatic factors, including the trauma type, presence of intracranial lesion, loss of consciousness, and Glasgow Coma Scale score, were not associated with spontaneous recovery. Conclusions: In this multi-center study, spontaneously recovery was achieved in 47.5% patients with traumatic unilateral SOP. Even mild head trauma can lead to permanent SOP. Ocular factors, including the angle of deviation and fundus torsion, may better predict spontaneous resolution than traumatic factors in patients with traumatic unilateral SOP.

8.
Mol Cell Toxicol ; : 1-10, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35069752

RESUMO

Background: Bacterial ghosts (BGs) are empty cell envelopes commonly generated using Gram-negative bacteria; they represent a potential platform for efficient adjuvant and vaccine delivery systems. However, the efficient production of BGs from bacteria in a short period of time is challenging. Objective: The purpose of this study was to investigate the possibility of producing BGs in the Gram-positive Bacillus subtilis using various chemicals, and the potential application of BGs as a novel immunomodulatory agent. Results: In this study, Bacillus subtilis ghosts (BSGs) were generated, for the first time to the best of our knowledge, using the minimum inhibitory concentration (MIC) of hydrochloric acid (HCl; 6.25 mg/mL), sulfuric acid (H2SO4; 3.125 mg/mL), and nitric acid (HNO3; 6.25 mg/mL). Among the BSGs generated using these chemicals, HCl-induced BSGs were completely DNA-free as confirmed by real-time polymerase chain reaction. Scanning electron microscopy showed the formation of transmembrane lysis tunnel structures in HCl-induced BSGs. Murine macrophages exposed to the HCl-induced BSGs at a concentration of 1 × 105 CFU/mL showed a cell viability of 97.8%. Additionally, HCl-induced BSGs upregulated the expression of pro-inflammatory cytokines including interleukin (IL)-1ß, tumor necrosis factor alpha, and IL-6. Furthermore, we found differences in the protein expression profiles between intact live bacteria and BSGs using two-dimensional electrophoresis coupled with peptide mass fingerprinting/matrix-assisted laser desorption/ionization-time of flight mass spectrometry analysis. Conclusion: These data suggest that the HCl-induced BSGs may be potentially safe and effective candidates for inactivated bacterial vaccines and/or immunostimulants. Supplementary Information: The online version contains supplementary material available at 10.1007/s13273-022-00221-5.

9.
World J Clin Cases ; 10(1): 388-396, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35071543

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) leakage at C1/2 in spontaneous intracranial hypotension (SIH) is rare. Subdural hematoma (SDH), a serious complication of SIH, may lead to neurological deficits. This report presents a case of SDH after spontaneous C1/2 CSF leakage, which was treated with a targeted epidural blood patch (EBP). CASE SUMMARY: A 60-year-old man with no history of trauma was admitted to our hospital with orthostatic headache, nausea, and vomiting. Brain computed tomography imaging revealed bilateral, subacute to chronic SDH. Brain magnetic resonance imaging (MRI) findings were SDH with dural enhancement in the bilateral cerebral convexity and posterior fossa and mild sagging, suggesting SIH. Although the patient underwent burr hole trephination, the patient's orthostatic headache was aggravated. MR myelography led to a suspicion of CSF leakage at C1/2. Therefore, we performed a targeted cervical EBP using an epidural catheter under fluoroscopic guidance. At 5 d after EBP, a follow-up MR myelography revealed a decrease in the interval size of the CSF collected. Although his symptoms improved, the patient still complained of headaches; therefore, we repeated the targeted cervical EBP 6 d after the initial EBP. Subsequently, his headache had almost disappeared on the 8th day after the repeated EBP. CONCLUSION: Targeted EBP is an effective treatment for SDH in patients with SIH due to CSF leakage at C1/2.

10.
Crit Care ; 26(1): 3, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983595

RESUMO

BACKGROUND: Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component's effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation. METHODS: Nationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality. RESULTS: The mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by - 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, - 1.3 to - 0.5%; p < 0.001), a significant but extremely small difference. However, mortality decreased greater in patients who received vitamin C for ≥ 5 days (vs 1-2 or 3-4 days) (15.8% vs 18.8% vs 18.3%; p < 0.001). Further, vitamin C was associated with a lower hospital mortality in patients with older age, multiple comorbidities, pneumonia, genitourinary infection, septic shock, and mechanical ventilation. Consistent findings were found for 90-day mortality. Moreover, vitamin C alone or in combination with thiamine was significantly associated with decreased hospital mortality. CONCLUSIONS: Intravenous vitamin C of ≥ 5 days was significantly associated with decreased hospital and 90-day mortality in sepsis patients. Vitamin C combined with corticosteroids and/or thiamine in specific sepsis subgroups warrants further study.


Assuntos
Sepse , Choque Séptico , Adolescente , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Mortalidade Hospitalar , Humanos , Masculino , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Tiamina/uso terapêutico
11.
Microorganisms ; 10(1)2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35056549

RESUMO

Hepatitis A virus (HAV) is a serious threat to public health worldwide. We used multiplex polymerase chain reaction (PCR)-based next-generation sequencing (NGS) to derive information on viral genetic diversity and conduct precise phylogenetic analysis. Four HAV genome sequences were obtained using multiplex PCR-based NGS. HAV whole-genome sequence of one sample was obtained by conventional Sanger sequencing. The HAV strains demonstrated a geographic cluster with sub-genotype IA strains in the Republic of Korea. The phylogenetic pattern of HAV viral protein (VP) 3 region showed no phylogenetic conflict between the whole-genome and partial-genome sequences. The VP3 region in serum and stool samples showed sensitive detection of HAV with differences of quantification that did not exceed <10 copies/µL than the consensus VP4 region using quantitative PCR (qPCR). In conclusion, multiplex PCR-based NGS was implemented to define HAV genotypes using nearly whole-genome sequences obtained directly from hepatitis A patients. The VP3 region might be a potential candidate for tracking the genotypic origin of emerging HAV outbreaks. VP3-specific qPCR was developed for the molecular diagnosis of HAV infection. This study may be useful to predict for the disease management and subsequent development of hepatitis A infection at high risk of severe illness.

12.
Surg Endosc ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35001223

RESUMO

BACKGROUND: Pheochromocytoma often carries a risk for perioperative hemodynamic instability (HDI). The aim of this study is to evaluate the risk factors of intraoperative HDI during minimally invasive posterior retroperitoneal adrenalectomy (PRA) for pheochromocytoma. MATERIALS AND METHODS: This retrospective study analyzed the prospectively collected data of 172 patients who underwent laparoscopic PRA or robotic PRA for pheochromocytoma between January 2014 and December 2020 at a single tertiary center. The patients were divided into two groups according to the intraoperative hypertensive event of systolic blood pressure (> 160 mmHg). The clinical manifestations and perioperative hemodynamic conditions were analysed. RESULTS: In the multivariate logistic regression analysis, the tumor size (> 3.4 cm) [OR 3.14, 95% confidence intervals (CI) (1.48-6.64), p = 0.003], type of preoperative alpha-blocker (selective type) [OR 3.9, 95% CI (1.52-10.02), p = 0.005], preoperative use of beta-blockers [OR 3.94, 95% CI (1.07-14.49), p = 0.039] and type of anesthesia [total intravenous anesthesia (TIVA) vs. balanced anesthesia (BA)] [OR 2.57, 95% CI (1.23-5.38), p = 0.012] were determined as independent risk factors of intraoperative hypertensive events during minimally invasive adrenalectomy. CONCLUSIONS: The type of anesthesia was independently associated with intraoperative HDI along with larger tumor size, type of preoperative alpha-blocker and the use of preoperative beta-blockers. TIVA increased the risk of intraoperative hypertensive events compared with BA. Thus, the consideration of the type of anesthesia prior to adrenal surgery for pheochromocytoma along with the use of preoperative non-selective alpha-blockers may be beneficial in minimizing the risk of intraoperative HDI.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35005800

RESUMO

BACKGROUND AND AIMS: Vibration-controlled transient elastography (VCTE) has shown good diagnostic performance in predicting fibrosis stages in patients with non-alcoholic fatty liver disease (NAFLD). However, an optimal diagnostic approach to detect advanced fibrosis in patients with NAFLD has not been established. APPROACH AND RESULTS: We prospectively collected data from 539 subjects who underwent liver biopsy at a single centre between January 2014 and December 2019. Diagnostic performance was estimated using the area under the receiver-operating characteristic curve (AUROC). Several models combining the fibrosis 4 index (FIB-4) score and liver stiffness measurement (LSM) were analysed to reduce the need for unnecessary liver biopsies. We observed significant fibrosis (≥F2), advanced fibrosis (≥F3) and cirrhosis (F4) in 173 (32.1%), 74 (13.7%) and 46 subjects (8.5%), respectively. The AUROCs (95% CI) for LSMs to diagnose ≥F2, ≥F3 and F4 were 0.82 (0.78-0.85), 0.92 (0.89-0.94) and 0.95 (0.93-0.97), respectively. Optimal LSM cut-off values were 6.7 (≥F2), 8.3 (≥F3) and 9.8 (F4) kPa. LSMs were affected by waist circumference, serum albumin and fibrosis stage (R2  = 0.315). Abdominal obesity, elevated transaminase, diabetes mellitus and high IQR/Median were associated with the discordance of ≥2 fibrosis stages between LSMs and histologic data. The sequential use of the age-adjusted FIB-4 and LSMs yielded the least uncertainty (5.3%) in classifying disease severity with the highest diagnostic accuracy (81%) among a variety of non-invasive test combinations. CONCLUSIONS: The sequential approach of age-adjusted FIB-4 and VCTE could represent a practical diagnostic strategy to detect advanced fibrosis in NAFLD (ClinicalTrials.gov #NCT02206841).

14.
Can J Cardiol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007707

RESUMO

We report the first transcatheter aortic valve (TAV)-in-TAV implantation of an ACURATE neo2 into a degenerated Lotus prosthesis. Despite the good final result in this case, TAV-in-TAV of the ACURATE neo2 into a Lotus prosthesis may not be the first choice, as potential pitfalls must be taken into account.

15.
Sci Rep ; 12(1): 818, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039529

RESUMO

Tendons have limited reparative ability and perform a relatively simple mechanical function via the extracellular matrix. Thus, the injured tendon might be treated successfully by stem cell transplantation. We performed a randomized, controlled study to investigate the effects of mesenchymal stem cell injection for treating partial tears in the supraspinatus tendon. We enrolled 24 patients with shoulder pain lasting more than 3 months and partial tears in the supraspinatus tendon. Participants were assigned to three groups: stem cells in fibrin glue, normal saline/fibrin glue mixture, and normal saline only, with which intra-lesional injection was performed. Pain at activity and rest, shoulder function and tear size were evaluated. For safety measures, laboratory tests were taken and adverse events were recorded at every visit. Participants were followed up at 6, 12 weeks, 6, 12 months and 2 years after injection. The primary outcome measure was the improvement in pain at activity at 3 months after injection. Twenty-three patients were included in the final analysis. Primary outcome did not differ among groups (p = 0.35). A mixed effect model revealed no statistically significant interactions. Only time significantly predicted the outcome measure. All participants reported transient pain at the injection site. There were no differences in post-injection pain duration or severity. Safety measures did not differ between groups, and there were no persistent adverse events. Stem cell injection into supraspinatus partial tears in patients with shoulder pain lasting more than 3 months was not more effective than control injections.ClinicalTrials.gov Identifier: NCT02298023.

16.
PLoS One ; 17(1): e0261448, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35061730

RESUMO

Despite the importance of Helicobacter pylori infection and portal hypertension (PH)-associated gastrointestinal (GI) diseases, such as esophageal varices and portal hypertensive gastropathy (PHG), the impact of H. pylori infection on PH-related GI complications has not yet been elucidated. This meta-analysis investigated the association between H. pylori infection and the risk of PH-related GI complications. An electronic search for original articles published before May 2020 was performed using PubMed, EMBASE, and the Cochrane Library. Independent reviewers conducted the article screening and data extraction. We used the generic inverse variance method for the meta-analysis, and Begg's rank correlation test and Egger's regression test to assess publication bias. A total of 1,148 cases of H. pylori infection and 1,231 uninfected controls were included from 13 studies. H. pylori infection had no significant association with esophageal varices [relative risk (RR) = 0.96, 95% confidence interval (CI) = 0.87-1.06 for all selected studies; RR = 0.95, 95% CI = 0.84-1.07 for cohort studies; odds ratio (OR) = 0.96, 95% CI = 0.60-1.54 for case-control studies]. Although H. pylori infection was significantly associated with PHG in case-control studies [OR = 1.86, 95% CI = 1.17-2.96], no significant differences were found in the cohort studies [RR = 0.98, 95% CI = 0.91-1.05] or all studies combined [RR = 1.18, 95% CI = 0.93-1.52]. In conclusion, H. pylori infection was not associated with the risk of PH-related GI complications. Clinicians should carefully treat cirrhotic patients with PH-related GI complications, regardless of H. pylori infection.

17.
J Control Release ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065158

RESUMO

Tumor-associated macrophages (TAMs), which dampen the therapeutic efficacy of cancer immunotherapy, are the key players in the immunosuppressive tumor microenvironment (TME). Therefore, reprogramming TAMs into tumoricidal M1 macrophages possesses considerable potential as a novel immunotherapy. However, the low bioavailability of polarization agents and limited accumulation of TAMs restrict their anti-tumor efficacy. In this study, we developed a polymer-based hypoxia-responsive nanocomplex to target TAMs in hypoxia for enhanced cancer immunotherapy. We synthesized a hypoxia-cleavable polymer poly(ethylene glycol)-azo-poly(l-lysine) (PEG-azo-PLL) and formulated a nanocomplex by simple mixing PEG-azo-PLL and poly(I:C). By mimicking in vitro hypoxia conditions, PEG-azo-PLL/poly(I:C) complexes could transform the physicochemical properties to enhance the delivery efficiency of poly(I:C) to tumor hypoxia, where M2-like TAMs are accumulated. Furthermore, PEG-azo-PLL/poly(I:C) could successfully reduce the population of M2-like TAMs in hypoxic tumors and promoted infiltration of CD8+ T cells in vivo, resulting in the favorable conversion of immunosuppressive TME. Finally, PEG-azo-PLL/poly(I:C) could elicit a significant in vivo anti-tumor effect in B16F10-bearing mice in addition to a prolonged survival time, demonstrating that the hypoxia-responsive nanocomplex PEG-azo-PLL/poly(I:C) is a promising approach for TAM reprogramming immunotherapy for solid tumors.

18.
Korean J Intern Med ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34991230

RESUMO

Background/Aims: The long-term effect of Helicobacter pylori eradication on the metabolic syndrome or diabetes are unclear. The aim of this study was to evaluate the effect of H. pylori eradication on glycemic control in type 2 diabetes mellitus (T2DM) or prediabetes mellitus (preDM). Methods: A total of 124 asymptomatic subjects with T2DM or preDM were divided into H. pylori-negative (n = 40), H. pylori-positive with non-eradicated (n = 34), and eradicated (n = 50) groups. We measured H. pylori status (culture, histology, and rapid urease test) and glycated hemoglobin A1c (A1C) levels and followed-up at the 1st year and the 5th year of follow-up. Results: The A1C levels significantly decreased in the eradicated group compared to the negative group and the non-eradicated groups (at the 1st year, p = 0.024; at the 5th year, p = 0.009). The A1C levels decreased in male, and/or subjects < 65 years of age in subgroup analyses (in male subjects, p = 0.047 and p = 0.020 at the 1st and the 5th year; in subjects < 65 years of age, p = 0.028 and p = 0.006 at the 1st and the 5th year; in male subjects < 65 years of age, p = 0.039 and p = 0.032 at the 1st and the 5th year). The eradication of H. pylori was related to the decrease in A1C values throughout the follow-up period, compared to the non-eradicated group (p = 0.017). Conclusions: H. pylori eradication was related to the decreasing of A1C levels in patients with T2DM or preDM over a long-term follow-up period, especially in male and subjects < 65 years of age.

19.
Gut ; 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34992134

RESUMO

OBJECTIVE: Alcohol-related liver disease (ALD) ranges from never-decompensated ALD (ndALD) to the life-threatening decompensated phenotype, known as alcohol-related hepatitis (AH). A multidimensional study of the clinical, histological and molecular features of these subtypes is lacking. DESIGN: Two large cohorts of patients were recruited in an international, observational multicentre study: a retrospective cohort of patients with ndALD (n=110) and a prospective cohort of patients with AH (n=225). Clinical, analytical, immunohistochemistry and hepatic RNA microarray analysis of both disease phenotypes were performed. RESULTS: Age and mean alcohol intake were similar in both groups. AH patients had greater aspartate amino transferase/alanine amino transferase ratio and lower gamma-glutamyl transferase levels than in ndALD patients. Patients with AH demonstrated profound liver failure and increased mortality. One-year mortality was 10% in ndALD and 50% in AH. Histologically, steatosis grade, ballooning and pericellular fibrosis were similar in both groups, while advanced fibrosis, Mallory-Denk bodies, bilirubinostasis, severe neutrophil infiltration and ductular reaction were more frequent among AH patients. Transcriptome analysis revealed a profound gene dysregulation within both phenotypes when compare to controls. While ndALD was characterised by deregulated expression of genes involved in matrisome and immune response, the development of AH resulted in a marked deregulation of genes involved in hepatocyte reprogramming and bile acid metabolism. CONCLUSIONS: Despite comparable alcohol intake, AH patients presented with worse liver function compared with ndALD patients. Bilirubinostasis, severe fibrosis and ductular reaction were prominent features of AH. AH patients exhibited a more profound deregulation of gene expression compared with ndALD patients.

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