Riisherrera3900
Our previous studies revealed that fibrin interacts with the VLDL receptor (VLDLR) through a pair of its βN-domains and this interaction promotes transendothelial migration of leukocytes and, thereby, inflammation. In agreement, the NDSK-II fragment representing the central part of the fibrin molecule and containing these domains stimulates leukocyte transmigration. However, the recombinant (β15-66)2 fragment corresponding to a pair of the βN-domains inhibits NDSK-II-stimulated leukocyte transmigration. To explain this paradox, we hypothesized that fibrin βN-domains have dual function in fibrin-dependent inflammation, namely, their C-terminal regions containing the VLDLR-binding sites promote leukocyte transmigration while their N-terminal regions are responsible for inhibition of this process. To test this hypothesis and to further clarify the molecular mechanisms underlying fibrin-induced VLDLR-dependent pathway of leukocyte transmigration and its inhibition, we prepared the dimeric (β15-44)2 and (β40-66)2 fragments corresponding to the N- and C-terminal regions of the βN-domains and studied their effect on endothelial permeability and transendothelial migration of leukocytes. The results obtained revealed that (β40-66)2 bound to the VLDLR with high affinity and promoted endothelial permeability and leukocyte transmigration while (β15-44)2 did not interact with this receptor and had no effect on leukocyte transmigration, in agreement with our hypothesis. We also found that the first three N-terminal residues of the βN-domains play a critical role in the inhibitory properties of these domains. Further, the inhibitory properties of the βN-domains were expressed only upon their isolation from the fibrin molecule. The question of whether their inhibitory function may play a role in fibrin remains to be addressed.The gut microbial ecosystem, which is a collection of the host-microbiota interactions and the inter-species interplay among bacteria-dominated microbiota, has become a research hotspot due to its contribution to host health in recent years. Lactobacillus, which has worldwide usage in fermented dairy products, has aroused increasing attention and becomes one of the commonly used probiotics given its promising applications in intestinal health and disease, though it occupies a relatively small proportion of the intestinal microbiota. In the review, we first update the current understanding of determinants of Lactobacillus abundance in the intestinal tract. We then review evidence from animal models to human trials that provided insights into Lactobacillus's applications in common intestinal disorders including the Helicobacter pylori infection, colorectal cancer, diarrhea, inflammatory bowel disease, and irritable bowel syndrome. Mechanisms underlying the probiotic role of Lactobacillus are finally discussed in five aspects microbial interactions, the improvement of intestinal barrier function, the immunoregulation, the anticancer activity, and the metabolic regulation. This review aims to yield a profound understanding of how Lactobacillus will contribute to disease prevention and individualized therapies in future clinical practice, and to inspire novel microbial strategies utilizing both probiotics and their products in the fields of biology and medicine.
Neuraxial ultrasonography can improve the technical performance of spinal anesthesia. However, there are no data regarding the optimal approach for ultrasound-assisted spinal anesthesia. This study aimed to compare the midline and paramedian approaches for ultrasound-assisted spinal anesthesia in adult orthopedic patients.
A single-center, prospective, randomized controlled trial.
Operating room.
One hundred and twelve patients undergoing orthopedic surgery were included.
Patients were randomized to undergo either the midline or paramedian approach for preprocedural ultrasound-assisted spinal anesthesia.
The primary outcome was the number of needle passes required for successful dural puncture. Secondary outcomes were the number of needle insertions, first pass/attempt success rate, procedural time, and the incidence of periprocedural complications.
The median number of needle passes was significantly lower in the paramedian group (1 [IQR, 1-2]) than in the midline group (3 [2-6]; P<0.001). The paramedian approach showed higher first pass/attempt success rates compared with the midline group (58.9% vs. AP-III-a4 purchase 21.4%; 91.1% vs. 53.6%; both, P<0.001). Total procedure times were significantly shorter in the paramedian group than in the midline group (113 [72.5-146.5] vs. 196 [138-298.5] seconds; P<0.001). The quality of sonographic images was graded as good in 94.6% of paramedian sagittal oblique views and 54.5% of transverse median views. No significant intergroup differences were found in the incidence of periprocedural complications.
Compared with the midline approach, the ultrasound-assisted paramedian approach showed improved efficacy in terms of the number of needle manipulations, first pass success rates, and procedural time. These results suggest that the paramedian approach may be more efficient for preprocedural ultrasound-assisted spinal anesthesia.
NCT03491943.
NCT03491943.Protein aggregation can affect the stability and function of proteins, and may lead to developing diseases, but reports on the in vivo effect of aggregates are scarce. In the current study, the effect of phenylalanine (Phe) and indole presence was first investigated on the structure and stability of human lysozyme (HLZ) and its aggregation under in vitro condition. Tm measurements, circular dichroism and spectrofluorimetric spectra, as well as and transmission electron microscopy (TEM) were performed in this stage. In the next step, pathogenicity of HLZ amorphous aggregates formed in presence or absence of the additives was investigated in vivo, by subcutaneous injection to adult male Wistar rats. Resulting inflamed tissues were studied by hematoxylin and eosin (HE), Congo red and Sudan black staining. Serum levels of liver enzymes (Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST)), specific inflammatory cytokines (Tumor Necrosis Factor Alpha (TNF-α) and Interleukin 6 (IL-6)) as well as glucose, cholesterol, and triglyceride levels were measured. Amorphous aggregates of HLZ caused inflammation and affected the number of fat cells, macrophages, cytokines, liver enzymes and glucose. Indole, that increases amorphous aggregates amount as shown with CD, fluorescence, and TEM experiments, leads into more severe inflammation. In presence of Phe, (which stabilizes HLZ structure) a markedly milder inflammatory state is observed in histological results and no increase could be detected in the inflammation-related parameters. In conclusion, amorphous aggregates of HLZ may be pathogenic in vivo, and presence of anti-aggregation compounds (such as Phe) can be effective in diminishing their deleterious manifestations.We selected Bacillus licheniformis NY1505 by screening a strain capable of producing α-glucosidase inhibitors in both aerobic and anaerobic environments in vitro and spore formation. To confirm whether this strain proliferates in the intestine and produces α-glucosidase inhibitor, the spores of this strain were administered to mice orally. As the results, it was confirmed that 107 cells and about 300 units of α-glucosidase inhibitor per 1 g feces were excreted in the feces after three weeks of administration as spores. And after two weeks of stopping administration, Bacillus licheniformis NY1505 in the intestine are cleared. This means that Bacillus licheniformis NY1505 steadily proliferated in the intestine and produced α-glucosidase inhibitors and excreted in the feces. Also, it has an advantage in its use as it can easily eliminate Bacillus licheniformis NY1505 from the intestine. This method of ingesting only microorganisms is a more efficient and new method than the existing method of administering an α-glucosidase inhibitor that consumes a large amount of purified product. This method shows a process in which microorganisms capable of proliferating in the intestine directly produce and supply specific secondary metabolites in the intestine.
Ovarian cancer is a very common gynecological malignant tumor. Natural products are important sources of chemotherapy drugs for ovarian cancer. Damnacanthal is an anthraquinone derivative with anti-cancer pharmacological properties.
This study aimed to investigate the mechanisms underlying damnacanthal's effects against ovarian cancer.
In vitro experiments, CCK8, colony formation and flow cytometry assays were used to evaluate the anti-ovarian cancer effect of damnacanthal on SKVO3 and A2780 cells. The wound healing tests and the transwell invasion assays were used to detect the migration and infiltration of ovarian cancer cells. Western Blot assays and immunofluorescence staining were used to measure autophagy levels. In vivo experiments, the anti-ovarian cancer effect of damnacanthal was further evaluated in a xenograft nude mouse model of SKVO3 cells.
Damnacanthal induced significant cell death and apoptosis, as well as significant inhibition in migration and invasion, in SKVO3 and A2780 cells, Furr growth being significantly inhibited comparably to the efficacy of cisplatin. Damnacanthal was also synergistic with cisplatin and showed inhibition in cisplatin-resistant ovarian cancer cells.
Damnacanthal inhibited the growth of ovarian cancer via the ERK/mTOR/autophagy signaling cascade, indicating that it may be a potential anti-ovarian cancer drug candidate.
Damnacanthal inhibited the growth of ovarian cancer via the ERK/mTOR/autophagy signaling cascade, indicating that it may be a potential anti-ovarian cancer drug candidate.
Paediatric tonsillar hyperplasia (TH) is associated with a spectrum of presentations ranging from recurrent tonsillitis (RT) to sleep-disordered breathing (SDB). The underlying pathogenesis of tonsillar hyperplasia remains poorly understood. Previous studies have implicated bacterial microcolonies as targets of host inflammatory cells and as a potential driver of the chronic inflammation seen in TH. The role of atopy in tonsillar hyperplasia is also largely unknown. In this study, we aimed to determine the allergic responses and microbial factors that may influence TH in children.
Paired tonsils and a serum sample were collected from 21 children undergoing tonsillectomy for RT or SDB in the Auckland region. The disposition of immunoglobulin isotypes (IgG, A, M and E) and local inflammatory cells on histological sections of tonsil tissue were determined using immunohistochemistry techniques. Aeroallergen specific IgE (sIgE) and Staphylococcal enterotoxin C specific IgE (SEC-specific IgE) were measured in sto determine the microbial composition of microcolonies in tonsil tissue. These findings enhance current understanding of the microbiology of tonsils in children with TH and have important implications for antibiotic strategies.
These results suggest that there is a local IgE response in children with TH. Local IgE production is unrelated to systemic atopy and may play a key role in the pathogenesis of TH. This is the first study to determine the microbial composition of microcolonies in tonsil tissue. These findings enhance current understanding of the microbiology of tonsils in children with TH and have important implications for antibiotic strategies.
