Search

Hypoxia represent a condition in which an adequate amount of oxygen supply is missing in the body, and it could be caused by a variety of diseases, including gastrointestinal disorders. This review is focused on the role of hypoxia in the maintenance of the gut homeostasis and related treatment of gastrointestinal disorders. The effects of hypoxia on the gut microbiome and its role on the intestinal barrier functionality are also covered, together with the potential role of hypoxia in the development of gastrointestinal disorders, including inflammatory bowel disease and irritable bowel syndrome. Finally, we discussed the potential of hypoxia-targeted interventions as a novel therapeutic approach for gastrointestinal disorders. In this review, we highlighted the importance of hypoxia in the maintenance of the gut homeostasis and the potential implications for the treatment of gastrointestinal disorders.

Recent investigations show that dietary consumption of flavonoids could potentially confer neuroprotective effects through a variety of direct and indirect mechanisms. Numerous flavonoids have been shown to cross the BBB and accumulate within the central nervous system (CNS). Some of these compounds purportedly counteract the accumulation and deleterious effects of reactive oxygen species, fostering neuronal survival and proliferation by inhibiting neuroinflammatory and oxidative stress responses. Moreover, several studies suggest that gut microbiota may participate in regulating brain function and host behavior through the production and modulation of bioactive metabolites. Flavonoids may shape gut microbiota composition by acting as carbon substrates to promote the growth of beneficial bacteria that produce these neuroprotective metabolites, consequently antagonizing or suppressing potential pathogens. By influencing the microbiota-gut-brain axis through this selection process, flavonoids may indirectly improve brain health. This review examines the current state of research into the relationship between bioactive flavonoids, gut microbiota, and the gut-brain axis.

Polysaccharides derived from plants, algae, or fungi serve as the major components of some human diets. Polysaccharides have been shown to exhibit diverse biological activities in improving human health, and have also been proposed to function as potent modulators of gut microbiota composition, thus playing a bi-directional regulatory role in host health. Here, we review a variety of polysaccharide structures potentially linked to biological functions, and cover current research progress in characterizing their pharmaceutical effects in various disease models, including antioxidant, anticoagulant, anti-inflammatory, immunomodulatory, hypoglycemic, and antimicrobial activities. We also highlight the effects of polysaccharides on modulating gut microbiota via enrichment for beneficial taxa and suppression of potential pathogens, leading to increased microbial expression of carbohydrate-active enzymes and enhanced short chain fatty acid production. This review also discusses polysaccharide-mediated improvements in gut function by influencing interleukin and hormone secretion in host intestinal epithelial cells.

Introduction: Most drug-eluting stents (DESs) inhibit intimal hyperplasia but impair re-endothelialization. This study aimed to evaluate in vivo strut coverage and neointimal growth in a new glycyrrhizin acid (GA)-eluting stent.Methods: New Zealand White rabbits (n = 20) with atherosclerotic plaques were randomly divided into three groups based on implanted iliac artery stents: bare-metal stents (BMSs), rapamycin-eluting stents, and GA-eluting stents. After the in vivo intravascular ultrasound (IVUS) assessment at 28 days, the vessels were harvested for scanning electron microscopy (SEM) and histology. After 4 weeks of follow-up, the stent and external elastic lamina (EEL) areas were compared among the groups.Results: The rapamycin- or GA-eluting stents significantly reduced the neointimal area compared with BMSs, though GA-eluting stents had the lowest reduction. There were more uncovered struts for rapamycin-eluting stents than those for GA-eluting stents and bare-metal stents. The endothelial nitric oxide synthase (eNOS) expression in GA-eluting stents was much higher than that in BMSs and rapamycin-eluting stents, even though the endothelial coverage between struts was equivalent between BMSs and GA-eluting stents. Moreover, GA-eluting stents markedly promoted re-endothelialization and improved arterial healing compared to rapamycin-eluting stents in a rabbit atherosclerotic model.Conclusion: In conclusion, the novel GA-coated stent used in this study inhibited intimal hyperplasia and promoted re-endothelialization.

In allogeneic hematopoietic cell transplantation (allo-HSCT), both virus-specific T cells and leukemia-specific T cells need to be reconstituted to protect patients from virus infections and primary disease relapse. Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allo-HSCT. Emerging data indicate that CMV reactivation is associated with reduced risk of leukemia relapse in patients with acute myeloid leukemia (AML) undergoing allo-HSCT. In a cohort of 24 WT1+ AML patients during the first year following HSCT, CMV specific CD8+ T cells (CMV-CTL) reconstituted much faster than WT1-specific CD8+ T cell (WT1-CTL) after allo-SCT. Moreover, CMV-CTL expressed lower levels of exhaustion markers and were more functional as identified by production of IFN-γ/TNF-α and expression of Eomes/T-bet. Interestingly, our patients with CMV reactivation presented higher frequency of CMV-CTL, lower levels of Eomes+T-bet- and higher levels of Eomes+T-bet+ expression in response to WT1 and CMV pp65 antigen during the first year after transplantation as compared to patients without CMV reactivation. Kinetics of CMV-CTL and WT1-CTL after transplantation might be associated with measurable residual disease and later leukemia relapse. Our results support that CMV reactivation, aside from the CMV-CTL reconstitution, could influence WT1-CTL reconstitution after allo-HSCT, thus potentially contributing to the remission/relapse of AML.

BackgroundMahaim-type accessory pathways (MAPs) are rare accessory pathways (APs) with specific properties. They are mostly located in the right side of the heart but rarely exist on the left side.ObjectivesThis study aims to analyze the clinical and electrophysiological (EP) characteristics of both-sided MAPs.MethodsA total of 2,249 patients with AP from our center were enrolled between 1 January 2011 and 27 March 2022. During the EP study (EPS) 17 patients were diagnosed with MAPs (right-sided: n = 13, left-sided: n = 4) according to the properties of Mahaim fibers.ResultsMAPs constitute 0.75% of all APs. Out of 1,553 patients with left-sided APs, four patients (0.26%) were diagnosed with Mahaim fiber-mediated tachycardia. Out of 696 patients with right-sided APs, 13 patients (1.9%) were diagnosed with Mahaim fiber. Most Mahaim fibers were located at the free wall of the tricuspid and mitral annuli. Seven patients of right-sided MAPs were of atriofasicular type, six patients had right-sided MAPs, and all of the patients with left-sided MAPs were of atrioventricular (AV) type. The M potential only was detected in long-length MAPs. Coexistence with other supraventricular tachycardias (SVTs) was also observed both in patients with right-sided and left-sided MAPs. All the patients underwent radiofrequency ablation successfully. Only one patient had tachycardia recurrence during a follow-up.ConclusionAlthough MAPs are commonly located at right sides, left sites are not impossible. The M potential contributes to the improvement of the successful ablation.

A 71-year-old female with a dual-chamber pacemaker presented to our hospital complaining of repeated chest pain. She was diagnosed with unstable angina. On day 7, the patient suddenly suffered cardiopulmonary arrest due to an inferior ST segment elevation myocardial infarction (STEMI). Pacemaker lost capture was suspected and was later confirmed by a pacemaker check with a high pacing threshold and a low sensing parameter. Emergency coronary angiography revealed that a large filling defect remained due to an extensive thrombus in the proximal left circumflex (LCX) with thrombolysis in myocardial infarction (TIMI) grade 2 flow, and then a repeat thrombus aspiration was performed. After reperfusion, the parameters of the right ventricular lead were gradually returned. We conclude that the loss of the right ventricular lead pacing occurred in this case of acute coronary syndrome (ACS) induced by an LCX thrombus due to an LCX supplying the right ventricular septal.

The grassland in the Qinghai–Tibetan plateau provide habitat for many indigenous and introduced ruminants which perform important ecological functions that impact the whole Qinghai–Tibetan plateau ecosystem. These indigenous Tibetan ruminants have evolved several adaptive traits to withstand the severe environmental conditions, especially cold, low oxygen partial pressure, high altitude, strong UV radiation, and poor forage availability on the alpine rangelands. Despite the challenges to husbandry associated with the need for enhanced adaptation, several domesticated ruminants have also been successfully introduced to the alpine pasture regions to survive in the harsh environment. For ruminants, these challenging conditions affect not only the host, but also their commensal microbiota, especially the diversity and composition of the rumen microbiota; multiple studies have described tripartite interactions among host-environment-rumen microbiota. Thus, there are significant benefits to understanding the role of rumen microbiota in the indigenous and introduced ruminants of the Qinghai–Tibetan plateau, which has co-evolved with the host to ensure the availability of specific metabolic functions required for host survival, health, growth, and development. In this report, we systemically reviewed the dynamics of rumen microbiota in both indigenous and introduced ruminants (including gut microbiota of wild ruminants) as well as their structure, functions, and interactions with changing environmental conditions, especially low food availability, that enable survival at high altitudes. We summarized that three predominant driving factors including increased VFA production, enhanced fiber degradation, and lower methane production as indicators of higher efficiency energy harvest and nutrient utilization by microbiota that can sustain the host during nutrient deficit. These cumulative studies suggested alteration of rumen microbiota structure and functional taxa with genes that encode cellulolytic enzymes to potentially enhance nutrient and energy harvesting in response to low quality and quantity forage and cold environment. Future progress toward understanding ruminant adaptation to high altitudes will require the integration of phenotypic data with multi-omics analyses to identify host-microbiota co-evolutionary adaptations enabling survival on the Qinghai–Tibetan plateau.

Congenital talipes equinovarus (CTEV) is one of the most common congenital limb defects in children, which is a multifactorial and complex disease that associates with many unknown genetic, social-demographic, and environmental risk factors. Emerging evidence proved that gene expression or mutation might play an important role in the occurrence and development of CTEV. However, the underlying reasons and involved mechanisms are still not clear. Herein, to probe the potential genes and related signaling pathways involved in CTEV, we first identified the differentially expressed genes (DEGs) by mRNA sequencing in pediatric patients with CTEV compared with normal children. The gene of COL1A2 was upregulated, and AKT3 was downregulated at the transcriptional level. Western blot and quantitative polymerase chain reaction (qRT-PCR) results also showed that the expression of COL1A2 in CTEV was enhanced, and the AKT3 was decreased. Furthermore, the COL1A2 Knock-in (+COL1A2) and AKT3 Knock-out (-AKT3) transgenic mice were used to verify the effects of these two genes in the CTEV, and the results of which showed that both COL1A2 and AKT3 were closely related to the CTEV. We also investigated the effect of the PI3K-AKT3 signaling pathway in CTEV by measuring the relative expression of several key genes using Western blot and qRT-PCR. In line with the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis data, the PI3K-AKT3 signaling pathway might play a potentially important role in the regulation of pathological changes of CTEV. This study will provide new ideas for the mechanism investigation and prenatal diagnosis of CTEV.

ObjectiveTo quantitatively evaluate the effectiveness of the Ponseti method for the correction of clubfoot, we decided to use magnetic resonance imaging (MRI) to evaluate changes in the tarsal bone relationship.MethodsThis is a retrospective study of fifteen children with clubfeet who were treated with the Ponseti method. MRI studies were obtained using a 3.0T Machine (GE Healthcare, United States). T1-weighted and T2-weighted images were acquired in the standard anatomic sagittal, transverse, and coronal planes. For the measurement, the best slice that clearly demonstrated the anatomy was chosen. Sagittal talocalcaneal angle, sagittal tibiocalcaneal angle, coronal tibiocalcaneal angle, transverse talar neck angle, transverse talonavicular angle, and transverse talocalcaneal angle were measured. The eighteen corrected clubfeet were compared with the twelve unilateral normal feet at clinical and radiological levels using a Pirani scoring system and MRI, respectively.ResultsIn total, 15 cases (twelve boys and three girls) with clubfeet were examined by using MRI. Twelve cases had unilateral and three had bilateral involvement (eleven left clubfeet and seven right clubfeet), giving a total of eighteen clubfeet when compared with twelve normal feet. The mean age of patients at examination was 47.7 months (8–96 months). The recovery of the corrected clubfoot in these patients met the goals of Ponseti treatment (functional, normal looking, pain-free, and plantigrade foot). Before Ponseti treatment, the mean Pirani score of clubfoot was 5.5 (5–6). During this follow-up, the Pirani score was 0.07 (0–0.05). The results of the MRI indicated that only the transverse talonavicular angle showed a significant difference between the treated clubfeet and the normal feet (p < 0.001). One case had dorsal talonavicular subluxation in the sagittal plane and had the lateral subluxation of the navicular in the transverse plane, which has never been reported in previous studies.ConclusionAlthough the appearance and function of clubfoot were recovered well after the Ponseti method, the results of MRI indicated that the Ponseti method successfully corrected the varus, cavus, and equinus deformities and incompletely corrected the adduction deformity regarding transverse talonavicular angle. At the same time, the Ponseti method may cause dorsal talonavicular subluxation in the sagittal plane and lateral subluxation of the navicular in the transverse plane on MRI.

Leptin is an adipocyte-derived hormone and maintains adipose function under challenged conditions. Autophagy is also essential to maintain cellular homeostasis and regulate characteristics of adipose tissue. However, the effects of leptin on autophagy of adipocyte remain elusive. Here, we demonstrated endoplasmic reticulum (ER) stress and leptin were correlated with autophagy and inflammation by transcriptome sequencing of adipose tissue. Leptin-mediated inhibition of autophagy was involved in upstream reduction of ER stress proteins such as Chop, GRP78, and Atf4, since blockage of autophagy using pharmacological approach had no effect on tunicamycin-induced ER stress. Moreover, we determined KLF4, the potential transcriptional factor of Atf4, was required for the leptin-mediated autophagy in the regulation of adipocyte inflammation. Importantly, ATF4 physically interacted with ATG5 and subsequently formed a complex to promote adipocyte autophagy. Further analysis revealed that Atg5, a core component of autophagosome, was the target for leptin-mediate autophagy. In addition, leptin alleviated ER stress-induced inflammation by reducing autophagy-mediated degradation of IκB in adipocytes. Exogenous leptin treatment also ameliorated autophagy and inflammation of white adipose tissue in ob/ob mice. Taken together, our results indicated that leptin inhibited ER stress-mediated autophagy and inflammation through the negatively regulation of Atf4/Atg5 complex in adipocytes. These findings identify a new potential means for intervention of autophagy to prevent or treat obese caused metabolic syndrome of mammals.