Journal of applied biomedicine最新文献

Background/aims: The functional lumen imaging probe (FLIP) relies on the principle of impedance planimetry that enables direct measurement of intraluminal pressure, cross-sectional areas, and wall biomechanical properties. The aim of our pilot project was to introduce this method to assess function of the lower oesophageal sphincter and pyloric muscle in experimental pigs.

Methods: All measurements were accomplished in one session in six adult female pigs (mean weight 34.2 ± 3.6 kg), using the EndoFLIP 1.0 System with EndoFLIP catheters. Five major parameters were evaluated: balloon pressure (mm Hg), estimated diameter (mm), cross-sectional area (mm2), distensibility (mm2/mm Hg), and zone compliance (mm3/mm Hg).

Results: In total, 180 readings were successfully accomplished. Most of the measured values were nearing lower average figures for the lower oesophageal sphincter, and upper average figures for the pylorus in healthy humans. The porcine pyloric sphincter is composed of the Torus pyloricus. It serves as a study "gatekeeper" between the stomach and D1 duodenum, thus explaining higher pyloric readings. There was a clear trend for increasing values of CSA (cross-sectional area), diameter, and balloon pressure with increased filling balloon volumes. However, the sphincter distensibility did not change with increasing filling volumes, either for the lower oesophageal sphincter or pylorus.

Conclusion: Endoscopic functional luminal planimetry in experimental pigs is feasible, both for the lower oesophageal sphincter and the pylorus. This is an important starting point for future experimental endoscopic trials and pharmacology studies.

Background: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus.

Objective: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.

Methods: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis.

Results: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions.

Conclusion: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.

Acute lymphoblastic leukemia (ALL) is the most common childhood hematological malignancy, but it also affects adult patients with worse prognosis and outcomes. Leukemic cells benefit from protective mechanisms, which are mediated by intercellular signaling molecules - cytokines. Through these signals, cytokines modulate the biology of leukemic cells and their surroundings, enhancing the proliferation, survival, and chemoresistance of the disease. This ultimately leads to disease progression, refractoriness, and relapse, decreasing the chances of curability and overall survival of the patients. Targeting and modulating these pathological processes without affecting the healthy physiology is desirable, offering more possibilities for the treatment of ALL patients, which still remains unsatisfactory in certain cases. In this review, we comprehensively analyze the existing literature and ongoing trials regarding the role of chemokines and interleukins in the biology of ALL. Focusing on the functional pathways, genetic background, and critical checkpoints, we constructed a summary of molecules that are promising for prognostic stratification and mainly therapeutic use. Targeted therapy, including chemokine and interleukin pathways, is a new and promising approach to the treatment of cancer. With the expansion of our knowledge, we are able to uncover a spectrum of new potential checkpoints in order to modulate the disease biology. Several cytokine-related targets are advancing toward clinical application, offering the hope of higher disease response rates to treatment.

Objective: This research investigated the effects of different hemodialysis modalities combined with low-calcium dialysate (LCD) on mineral metabolism and vascular calcification (VC) in maintenance hemodialysis (MHD) patients with chronic kidney disease (CKD).

Methods: General data were collected from 192 cases of MHD patients, who were divided into 4 groups according to the randomized numerical table. Each group was given LCD treatment, and conventional hemodialysis (HD), high-flux HD (HFHD), hemodiafiltration (HDF), and HD + hemoperfusion (HP) were performed, respectively. The patients were dialyzed 3 times per week for 4 h each time, and each group was treated for 6 months. Fasting venous blood was collected. Serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitive C-reactive protein (hs-CRP) levels were measured by ELISA, calcium (Ca2+), phosphorus (P), Ca2+-P product, serum creatinine (SCr), blood urea nitrogen (BUN), β2 microglobulin (β2-MG), and intact parathyroid hormone (iPTH) were measured by chemiluminescence immunoassay, serum alkaline phosphatase (ALP) was determined by turbidimetric assay, and 25-hydroxyvitamin D (25(OH)D) was measured by autoradiographic immunoassay. To assess the extent of calcification in the iliac artery and abdominal aorta, a multilayer spiral CT device was employed for abdominal scans.

Results: Serum IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP levels decreased, while 25(OH)D levels increased in the four groups after treatment. The most pronounced effect on the reduction of IL-6, hs-CRP, TNF-α, Ca2+, P, Ca2+-P product, SCr, BUN, β2-MG, iPTH, and ALP was in the HD + HP group, followed by the HDF and HFHD groups, and then by the HD group. The rate of VC in the HDF, HFHD, and HD + HP groups was lower than that in the HD group, and the rate in the HD + HP group was lower than that in the HDF and HFHD groups.

Conclusion: The combination of HD + HP and LCD in treating CKD with MHD is effective, evidently rectifying disruptions in serum Ca2+ and P metabolism, enhancing kidney function, lessening the body's inflammatory response, and lessening VC.

Linoleic acid (LA), an essential fatty acid, has emerged as a pivotal regulator in disorders associated with inflammation in recent years; however, the underlying mechanisms are still not completely understood. We utilized network pharmacology and experimental methodologies to elucidate the mechanisms underlying the anti-inflammatory effects of LA. Our network pharmacology analysis revealed that LA shares common targets with sepsis. These targets are enriched in various pathways comprising C-type signaling pathway, PI3K-Akt signaling pathway, toll-like receptor signaling pathway, neutrophil extracellular trap formation, AMPK signaling pathway, and autophagy-animal. These findings suggest that LA may exert regulatory effects on inflammation and autophagy during sepsis. Subsequently, we established in vivo and ex vivo models of sepsis using lipopolysaccharide (LPS) in experimental study. Treatment with LA reduced lung damage in mice with LPS-induced lung injury, and reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma, bronchoalveolar lavage fluid (BALF), and peritoneal lavage fluid (PLF). LA also decreased the production of TNF-α and IL-6 in RAW264.7 macrophages exposed to LPS. In LPS-induced RAW264.7 macrophages, LA induced an elevation in LC3-II while causing a reduction in p62, which was associated with downregulation of toll-like receptor 4 (TLR4). We utilized 3-methyladenine (3-MA) to inhibit the autophagic activity, which reversed the modulatory effects of LA on LC3-II and p62. 3-MA also prevented the decline in TLR4 expression along with reduction in pro-inflammatory cytokines secretion. Our findings suggest that the activation of autophagy by LA may lead to the downregulation of TLR4, thereby exerting its anti-inflammatory effects.

Background: Metabolic syndrome is a significant pro-inflammatory and pro-coagulant condition. The clinical association of adiponectin, a mainly antidiabetogenic molecule, and its interaction with platelets and platelet indices remains insufficiently investigated.

Objective: The aim of our study was to investigate the association of adiponectin with platelets and platelet indices in patients with metabolic syndrome.

Methods: The investigation was conducted as a cross-sectional study involving 113 subjects: 63 patients with the diagnosis of metabolic syndrome, and 50 healthy controls - with clear inclusion and exclusion criteria. The group of patients with metabolic syndrome was divided into two subgroups according to the platelet/high-density lipoprotein (HDL) ratio.

Results: The subgroup with a higher platelet/HDL ratio was prediabetic. In the same subgroup of patients, a positive correlation between the adiponectin and mean platelet volume (MPV) was seen, while linear regression (95% CI) confirmed the association.

Conclusion: Considering that MPV is the index that indicates average platelet volume and activity, we believe this association with adiponectin can represent a protective compensatory response in patients with metabolic syndrome and prediabetes. Our results provide a basis for a more precise selection of patients in whom the future therapeutic application of recombinant adiponectin would be most effective.

Anti-N-methyl D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder characterized by IgG antibodies targeting NMDAR. The prevalence is remarkably higher in women and some develop the condition during pregnancy. While immunotherapies have shown good outcomes for pregnant mothers and their infants, the impact on early neurodevelopment remains elusive. This study investigates the effects of anti-NMDAR antibody on the development of primary cortical cultures. Anti-NMDAR antibody was administered to the cultures at day in vitro 5 for the following 5 days to assess dendritic branching and arbor complexity, and at day in vitro 14 for measuring the expression of brain-derived neurotrophic factor (BDNF) and synaptic proteins. Immature cultured neurons treated with anti-NMDAR antibody exhibited impaired dendritic branching and arbor complexity. Interestingly, BDNF expression was unaffected in mature neurons. Additionally, GluN1 expression, a mandatory NMDAR subunit, was significantly reduced, while no significant alterations were observed in PSD-95, gephyrin and synaptophysin expression. These findings shed light on the structural and synaptic impacts of anti-NMDAR antibody on immature neurons, providing evidence for their consequences in early neuronal development.

Cell senescence is intensively related to aging and neurodegenerative diseases. This study aimed to explore the effect and targets of Astragaloside IV against amyloid-beta-induced astrocyte senescence. Oligomerized amyloid-beta was prepared to culture with human astrocytes. The effects of Astragaloside IV were assessed based on SA-β-gal staining analysis, senescence markers (p53, p16INK4, and p21WAF1), neurotrophic growth factor levels (qRT-PCR), and cell proliferation (CCK-8 kit). The targets for Astragaloside IV were predicted, and hsp90aa1 protein was verified using molecular docking. After hsp90aa1 overexpression, the effects of Astragaloside IV on amyloid-beta-induced astrocytes were assessed. Treatment of human amyloid-beta-induced astrocytes with Astragaloside IV can decrease the percentage of SA-β-gal positive cells, downregulate the p53, p16INK4, and p21WAF1 levels, and increase the levels of neurotrophic growth factors (IGF-1 and NGF mRNA) and cell proliferation. Based on target prediction, hsp90aa1 was found to be a potential target of Astragaloside IV. Moreover, cellular experiments demonstrated that exogenously enhanced expression of hsp90aa1 overexpression suppressed the protective effect of Astragaloside IV on amyloid-beta-induced human astrocytes. The results presented here demonstrate that Astragaloside IV could confront amyloid-beta-induced astrocyte senescence via hsp90aa1, possibly opening new therapeutic avenues.

Cancer research is linked to modern life-sciences, encompassing achievements in virology, yeast-biology, molecular-biology, genetics, systems-biology, bioinformatics, and so on. With these fascinating developments, it's easy to overlook that the fundamental theories and treatment strategies were established in the early 20th century and have remained valid ever since. Therefore, tribute must be paid to the founders of the field. The main hypotheses on carcinogenesis, the genetic model and the metabolic model, and the concept of cancer-treatment with cytotoxic, targeted or metabolic drugs were proposed more than 100 years ago by great minds such as T. Boveri, O. Warburg, and P. Ehrlich. Hence nothing about these cancer concepts is really new. Through development of powerful new technologies, we have been able to decipher the mechanisms of malignant transformation, thus significantly advancing the field. Our own studies have been focused on the cross-talk between cell-growth-signaling and lipid-metabolism in ovarian cancer to find crossover-points for co-targeting in order to achieve synergistic treatment effects. Notably, a side-effect of the application of current methods of molecular-cell-biology is a deeper knowledge of the laws of normal cell-biology and cell-life. Thus we anticipate the field will advance rapidly in the near future.

Objectives: Olfactory dysfunction (OD) is a common symptom associated with Covid-19. During the Covid-19 pandemic, the importance of psychophysical olfactory tests and electrophysiological olfactory assessment increased. The purpose of the study was to analyze the psychophysical olfactory tests and the post-covid curves of olfactory event-related potentials (OERPs) and trigeminal event-related potentials (TERPs).

Methods: The prospective study included 98 subjects (62 females / 36 males). The average age was 42 years (range 21-84 years). Group I (n = 77) contained participants who had been infected with Covid-19. They were enrolled in the study at least 1 year after Covid-19. Group II (n = 21) was the healthy normosmic control group.

Results: In Group I, the OERPs of 18% participants were absent. Patients in Group I were statistically more likely to have an absence of OERPs (p = 0.036) than subjects in Group II. We did not detect a statistical difference in amplitudes and latencies of the OERPs between Group I and Group II. In Group I, N1 latency of the TERPs was significantly longer (p = 0.002) than in Group II. The amplitude of the N1-P2 interval of the TERPs was significantly lower (p = 0.025) in Group I than in Group II. According to the psychophysical Sniffin stick identification test, hyposmia was detected in 39% in Group I versus 0% in the control Group II.

Conclusion: OD is a common post-covid symptom. The presence of OERPs is a significant prognostic factor for olfactory function after Covid 19. We detected a lower percentage of absence of OERPs after Covid-19 compared to the previously published studies of post-viral OD and post-infectious OD. For TERPs, we detected a longer N1 latency and a lower amplitude for the N1-P2 interval after Covid-19. OERPs and TERPs can be considered valid biomarkers to evaluate the progress of post-covid OD.