Significant Time-dependent Decrease Research Articles

New physiological insights using multi-TE ASL MRI measuring blood-brain barrier water exchange after caffeine intake.

Caffeine, a known neurostimulant and adenosine antagonist, affects brain physiology by decreasing cerebral blood flow. It interacts with adenosine receptors to induce vasoconstriction, potentially disrupting brain homeostasis. However, the impact of caffeine on blood-brain barrier (BBB) permeability to water remains underexplored. This study investigated the water exchange via the BBB in a perturbed physiological condition caused by caffeine ingestion, using the multiple echo time (multi-TE) arterial spin labeling (ASL) technique. Ten healthy, regular coffee drinkers (age = 31 ± 9years, 3 females) were scanned to acquire five measurements before and six measurements after caffeine ingestion. Data were analyzed with a multi-TE two-compartment model to estimate exchange time (Tex), serving as a proxy for BBB permeability to water. Additionally, cerebral blood flow (CBF), arterial transit time (ATT), and intravoxel transit time (ITT) were investigated. Following caffeine intake, mean gray matter CBF showed a significant time-dependent decrease (P < 0.01). In contrast, Tex, ATT, and ITT did not exhibit significant time-dependent change. However, a non-significant decreasing trend was observed for Tex and ITT, respectively, while ATT showed an increasing trend over time. The observed decreasing trend in Tex after caffeine ingestion suggests a potential increase in water flux across the BBB, which may represent a compensatory mechanism to maintain brain homeostasis in response to the caffeine-induced reduction in CBF. Further studies with larger sample sizes are needed to validate and expand upon these findings.

Anti-Inflammatory Effects of Clarstatin, a Shared-Epitope-Antagonistic Cyclic Peptide, on Experimental Autoimmune Uveitis in Mice.

Polymorphism and mutations of human leukocyte antigens (HLAs) and calreticulin are risk factors for uveitis. Here, we sought to determine the therapeutic effects of Clarstatin, a cyclic peptide antagonist of the HLA shared-epitope-calreticulin interaction, in experimental autoimmune uveitis (EAU) models. Mice were injected with Clarstatin intraperitoneally and its effect was compared to that of corticosteroid. EAU was evaluated clinically and histologically. Ocular infiltration of CD45+ hematopoietic cells and splenocyte CD4+ expression were determined using immunofluorescence and flow cytometry (fluorescence-activated cell sorting [FACS]). ELISA was used to measure the ocular level of the proinflammatory cytokines. Clarstatin significantly ameliorated the severity of EAU in the C57BL/6J mild and the B10.RIII severe mice models. There was a significant dose and time-dependent decrease, in the range of 30% to 80%, in the clinical score (P < 0.05), histological score (P < 0.05), and number of retinal and spleen CD45+ cells (P < 0.05 and P < 0.001, respectively), a comparable effect to corticosteroid. Clarstatin reduced the intraocular levels of interleukin 6 (IL-6; P < 0.05) and monocyte chemoattractant protein-1 (MCP-1; P < 0.01) by 41% and 59%, respectively. Systemic delivery of Clarstatin significantly improved mild and severe EAU. Its potential anti-inflammatory therapeutic effects represent a novel mode of treatment in ocular inflammation. It may also be a relevant treatment modality in systemic autoimmune conditions in which calreticulin plays a role in their pathogenesis.

Hematological Changes in Newly Diagnosed Pulmonary Tuberculosis Patients on Standard Anti-TB Treatment Regimen and their Influence on Smear Conversion

Pulmonary tuberculosis (PTB) mortality remains high despite the availability of effective anti-TB therapy. Disease and treatment-associated hematological derangements at diagnosis and during therapy might contribute to this high TB mortality rate. This paper aims to determine hematological changes in newly diagnosed pulmonary tuberculosis patients on standard anti-TB treatment regimen and their influence on smear conversion. The study adopted a longitudinal design in which 55 newly diagnosed HIV negative PTB patients were followed up to the fifth month of anti-TB therapy. Blood samples (5ml) were collected for diagnosis during the second and fifth months and analyzed using automated HumaCount 5D hematology analyzer. Data was analyzed using Kruskal-wallis test with Dunn’s multiple comparisons test in Graph-Pad prism version 6.0. Throughout therapy, there was a statistically significant time-dependent decrease in median total white blood cell counts from 6.82x103/ uL at diagnosis to 5.87x103/ uL at the fifth month (P=0.0358). This decrease in total WBC count was majorly driven by significant decrease in the neutrophil numbers from 4.31x103/ uL at diagnosis to 2.97x103/ uL at the fifth month. The proportion of patients who had anemia at the fifth month of treatment increased compared to the second month post intensive phase. There was also a significant decrease in MCV, MCH and MCHC at the second month compared to diagnosis. Moreover, the median platelet count, MPV, PDW and PCT% decreased from 314x103/ uL, 8.9 fL, 10.4 fL and 0.273 at diagnosis to 232x103/ uL, 10.15 fL, 12.5 fL and 0.235 at the fifth month, respectively. High WBC count, high platelet count, low lymphocyte count and low HGB at the end of month two of therapy were shown to increase the likelihood of sputum non-conversion (OR-2.42 (95% Ci 2.07-2.82)), (OR-1.5 (95% Ci 1.01-2.22)), (OR-1 (95% Ci 1-1)) and (OR-2.58 (95% Ci 1.68-3.95)), respectively (P&lt;0.05). A significant number of PTB patients presented with anemia, thrombocytosis and leukocytosis. The proportion of patients with anemia increased over time. The study recommends screening for hematological abnormalities in patients for tailored patient interventions for better clinical outcomes.

Astaxanthin Supplementation Does Not Alter Training-Related Changes in Inflammatory Cytokine Profile in Arabian Racing Horses.

This study aimed to evaluate the oral supplementation of astaxanthin (ATX) on inflammatory markers in 3-year-old Arabian racehorses. Despite the recognized antioxidant and anti-inflammatory properties of ATX observed in vitro in rodent models and in human athletes, the effects in equine subjects remain unknown. This study involved a controlled trial with 14 horses receiving either ATX (six horses) or a placebo (eight horses), monitored over four months of race training. Inflammatory cytokines: TNFα, IFNγ, IL-6, IL-10, and prostaglandin E (PGE), were measured monthly to assess the impact of ATX on the inflammatory response. The results indicated no significant differences in measured parameters between the ATX and the control group during the study. However, a significant time-dependent decrease in TNFα and IFNγ levels (p = 0.001) was observed in both groups, suggesting that regular training naturally modulates inflammatory responses. Moreover, positive correlations were noted between TNFα and IFNγ (p < 0.001) in the early phase of the study and between IL-6 and IL-10 (p = 0.008) in the later phase. Hematological parameters remained stable and within reference ranges, indicating no adverse effects of ATX supplementation. Performance metrics, including the number of races completed and wins, showed no significant differences between groups, suggesting that ATX did not enhance athletic performance under the study conditions. Overall, while ATX supplementation affected neither cytokine levels nor performance in Arabian racehorses, the natural anti-inflammatory effects of regular training were evident. Further research is needed to explore potential benefits of ATX supplementation under different conditions, such as in horses with subclinical inflammation or varying training regimens, to fully clarify its role and applications in equine sports medicine.

Effectiveness of the flash glucose monitoring system in preventing severe hypoglycemic episodes and in improving glucose metrics and quality of life in subjects with type 1 diabetes at high risk of acute diabetes complications

AimsTo assess the effectiveness of the intermittent-scanned continuous glucose monitoring (isCGM) system in preventing severe hypoglycemic episodes and in improving glucose parameters and quality of life.MethodsFour hundred T1D individuals were enrolled in a prospective real-word study with an intermittently scanned continuous glucose monitoring device during the 12-months follow-up. The primary endpoint was the incidence of severe hypoglycemic events.Results82% of subjects were naïve to the use of the device (group A) and 18% were already wearing the system (group B). The cumulative incidence of severe hypoglycemia (SH) at 12 months was 12.06 per 100 person-year (95% CI: 8.35–16.85) in group A and 10.14 (95% CI: 4.08–20.90) in group B without inter-group differences. In group A there was a significant decrease in SH at 12 months compared to 3 months period (p = 0.005). Time in glucose range significantly increased in both groups accompanied with a significant decrease in glucose variability. HbA1c showed a progressive significant time-dependent decrease in group A. The use of the device significantly improved the perceived quality of life.ConclusionThis study confirmed the effectiveness of the isCGM in reducing hypoglycemic risk without glucose deterioration, with potential benefits on adverse outcomes in T1D individuals.Trial registration: ClinicalTrials.gov registration no. NCT04060732.

Degradation of Toxins Derived from Foodborne Pathogens by Atmospheric-Pressure Dielectric-Barrier Discharge.

Foodborne diseases can be attributed not only to contamination with bacterial or fungal pathogens but also their associated toxins. Thus, to maintain food safety, innovative decontamination techniques for toxins are required. We previously demonstrated that an atmospheric-pressure dielectric-barrier discharge (APDBD) plasma generated by a roller conveyer plasma device is effective at inactivating bacteria and fungi in foods. Here, we have further examined whether the roller conveyer plasma device can be used to degrade toxins produced by foodborne bacterial pathogens, including aflatoxin, Shiga toxins (Stx1 and Stx2), enterotoxin B and cereulide. Each toxin was spotted onto an aluminum plate, allowed to dry, and then treated with APDBD plasma applied by the roller conveyer plasma device for different time periods. Assessments were conducted using a competitive enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results demonstrate a significant time-dependent decrease in the levels of these toxins. ELISA showed that aflatoxin B1 concentrations were reduced from 308.6 µg/mL to 74.4 µg/mL within 1 min. For Shiga toxins, Stx1 decreased from 913.8 µg/mL to 65.1 µg/mL, and Stx2 from 2309.0 µg/mL to 187.6 µg/mL within the same time frame (1 min). Enterotoxin B levels dropped from 62.67 µg/mL to 1.74 µg/mL at 15 min, and 1.43 µg/mL at 30 min, but did not display a significant decrease within 5 min. LC-MS/MS analysis verified that cereulide was reduced to below the detection limit following 30 min of APDBD plasma treatment. Taken together, these findings highlight that a range of foodborne toxins can be degraded by a relatively short exposure to plasma generated by an APDBD using a roller conveyer device. This technology offers promising advancements in food safety, providing a novel method to alleviate toxin contamination in the food processing industry.

Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.

Chronic immune activation in tuberculosis (TB) associated with human immunodeficiency virus (HIV) infection (HIV/TB) modifies their clinical course. We prospectively measured osteopontin (OPN), full-length galectin-9 (FL-Gal9), and total-Gal9 (T-Gal9) levels in 32 patients with HIV/TB coinfection treated with anti-tuberculosis and antiretroviral therapies over 6-18 months to determine the amelioration of inflammatory conditions in response to the therapies. We observed a significant time-dependent decrease in FL-Gal9 in both pulmonary TB (PTB, n = 20) and extrapulmonary TB (EPTB, n = 12) patients. The levels of T-Gal9, OPN, and CRP decreased significantly after treatment in only PTB patients. We calculated the inflammatory score (INS) indicating immunologic recovery based on the decline in OPN, FL-Gal9, T-Gal9, and CRP levels. Baseline levels of T-Gal9 and OPN positively correlated with INS in all TB and only PTB patients, respectively, indicating that their levels predict better recovery. In contrast, FL-Gal9 levels at the second visit negatively correlated with INS in EPTB patients. The decrease rate in OPN levels at the second visit also correlated positively with INS in PTB patients. Women showed a higher INS and lower levels of FL-Gal9 than men. The patients with moderate grade severity on chest X-ray had higher CD4 cell numbers than those with limited grade severity. Monitoring these markers will help to predict and assess the response to therapy as well as to devise strategies to reduce the complications caused by chronic immune activation in patients with HIV/TB coinfection.

Long-term course of neutralising antibodies against SARS-CoV-2 in vaccinated and unvaccinated staff and residents in a Swiss nursing home: a cohort study 2021-2022.

Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. Our study comprised 45 participants, of which 39 were healthcare workers and six were residents. All participants were offered a maximum of three mRNA vaccine doses (Pfizer/BioNTech, BNT162b2) in December 2020, January 2021, and November/December 2021. Thirty-five participants received three vaccinations, seven either one or two, and three remained unvaccinated. We collected four blood samples: one in March 2021 and three during follow-ups in November 2021, February 2022, and June 2022. We performed a multifactorial serological SARS-CoV-2 assay (ABCORA) for immunoglobulin G, A, and M responses to spike (receptor-binding domain, S1, and S2) and nucleocapsid (N) proteins. Furthermore, we assessed predicted neutralisation activity based on signal over cutoff in ABCORA. We collected epidemiological data from participants via a standardised questionnaire. Thirty-two (71%) of the 45 participants showed hybrid immunity from combined vaccination and previous infection; 10 (22%) had only vaccine-induced immunity; and three (7%) had only post-infection immunity. Participants with hybrid immunity showed the highest predicted neutralisation activity at the end of the study period (median Sum S1 = 273), and unvaccinated participants showed the lowest (median Sum S1 = 41). Amongst participants who reported a SARS-CoV-2 infection, median Sum S1 levels increased with the number of vaccinations (p = 0.077). The healthcare worker group showed a significant time-dependent decrease in median Sum S1 after base immunisation (93% decrease, p = 0.0005) and the booster dose (26% decrease, p = 0.010). Predicted neutralisation activity was lower amongst residents (adjusted ratio of means [AM] = 0.7, 95% confidence interval [CI] = 0.3-1.0) and amongst smokers (AM = 0.5, 95% CI 0.3-0.8). Activity increased with the number of vaccinations (booster: AM = 3.6, 95% CI 1.5-8.8; no booster: AM = 2.3, 95% CI 0.9-2.5). Positive SARS-CoV-2 infection status tended to confer higher predicted neutralisation levels (AM = 1.5, 95% CI 0.9-2.5). Our study of the long-term serological course of SARS-CoV-2 in a nursing home showed that the first SARS-CoV-2 booster vaccine was essential for maintaining antiviral antibody levels. Hybrid immunity sustained SARS-CoV-2 immunity at the highest level. In critical settings such as nursing homes, monitoring the SARS-CoV-2 immune status may guide booster vaccinations.

Individualized Housing Modifies the Immune-Endocrine System in CD1 Adult Male Mice.

In the last years, different research groups have made considerable efforts to improve the care and use of animals in research. Mice (Mus musculus) are the most widely used animal species in research in the European Union and are sociable and hierarchical creatures. During experiments, researchers tend to individualize males, but no consideration is given to whether this social isolation causes them stress. The aim of this study was, therefore, to explore whether 4 weeks of social isolation could induce changes in different physiological parameters in adult Crl:CD1(ICR) (CD1) males, which may interfere with experimental results. Body weight, blood cells, and fecal corticosterone metabolites levels were the analyzed parameters. Blood and fecal samples were collected at weeks 1 and 4 of the experimental procedure. Four weeks of single housing produced a significant time-dependent decrease in monocytes and granulocytes. Fecal corticosterone metabolite levels were higher in single-housed mice after 1 week and then normalized after 4 weeks of isolation. Body weight, red blood cells, and platelets remained unchanged in both groups during this period. We can, therefore, conclude that social isolation affects some immune and endocrine parameters, and that this should be taken into account in the interpretation of research data.

Anticarcinogenic impact of extracellular vesicles (exosomes) from cord blood stem cells in malignant melanoma: A potential biological treatment.

Incidence of Malignant Melanoma has become the 5th in the UK. To date, the major anticancer therapeutics include cell therapy, immunotherapy, gene therapy and nanotechnology-based strategies. Recently, extracellular vesicles, especially exosomes, have been highlighted for their therapeutic benefits in numerous chronic diseases. Exosomes display multifunctional properties, including inhibition of cancer cell proliferation and initiation of apoptosis. In the present in vitro study, the antitumour effect of cord blood stem cell (CBSC)-derived exosomes was confirmed by the CCK-8 assay (p < 0.05) on CHL-1 melanoma cells and improve the repair mechanism on lymphocytes from melanoma patients. Importantly, no significant effect was observed in healthy lymphocytes when treated with the exosome concentrations at 24, 48 and 72 h. Comet assay results (OTM and %Tail DNA) demonstrated that the optimal exosome concentration showed a significant impact (p < 0.05) in lymphocytes from melanoma patients whilst causing no significant DNA damage in lymphocytes of healthy volunteers was 300 μg/ml. Similarly, the Comet assay results depicted significant DNA damage in a melanoma cell line (CHL-1 cells) treated with CBSC-derived exosomes, both the cytotoxicity of CHL-1 cells treated with CBSC-derived exosomes exhibited a significant time-dependent decrease in cell survival. Sequencing analysis of CBSC exosomes showed the presence of the let-7 family of miRNAs, including let-7a-5p, let-7b-5p, let-7c-5p, let-7d-3p, let-7d-5p and two novel miRNAs. The potency of CBSC exosomes in inhibiting cancer progression in lymphocytes from melanoma patients and CHL-1 cells whilst causing no harm to the healthy lymphocytes makes it a potential candidate as an anticancer therapy.

DDEL-10. ULTRASOUND-ENHANCED DRUG DELIVERY IN HUMANS ALTERS ENDOTHELIAL PHENOTYPE AND PERTURBS THE ULTRASTRUCTURE OF THE BLOOD BRAIN BARRIER

Abstract The use of low-intensity pulsed ultrasound with concomitant injection of microbubbles (LIPU/MB) achieves local and reversible opening the blood-brain barrier (BBB), enhancing the delivery of systemically administered drugs to the brain parenchyma. Electron microscopic studies conducted in animals proposed that LIPU/MB enhances paracellular diffusion across the cerebral vasculature, by disrupting tight junction proteins between endothelial cells, as well as enhancement of caveolar transcytosis. The effects of LIPU/MB on the ultrastructure of the human BBB and cerebral endothelial phenotype have not been systematically investigated. Here we report a first in-human electron microscopic study, examining endothelial phenotype and BBB ultrastructure in the peri-tumoral brain of humans after undergoing LIPU/MB-enhanced drug delivery. Non-eloquent peritumoral brain was biopsied at different time points (4-63 minutes) following an intraoperative LIPU/MB procedure in three patients who underwent a surgical resection of recurrent glioblastoma through a phase I clinical trial [NCT04528680]. Transmission electron microscopy was used to examine cross sections of the microvasculature and associated components of the BBB. We observed a significant (P = 0.0397) time-dependent decrease in the frequency of endothelial caveolae immediately after sonication compared to non-sonicated control vessels, which resolved within 1 hour of treatment. We also observed a time-dependent increase in membrane-bound vacuoles in the endothelial cytoplasm following sonication (P = 0.0002, one-way ANOVA). Sonicated blood vessels occasionally showed swollen astrocytes, convoluted luminal protections, and lightening of otherwise dense tight junction proteins, not frequently observed in non-sonicated biopsies from the same patients. Our study shows that LIPU/MB changes the endothelial phenotype within the cerebral vasculature, and suggests the accumulation of vacuoles in endothelial cells after BBB opening.

The distribution pattern of M2 and Adrenergicα2 receptors on inferior colliculi in male newborns of diabetic rats

AimsDespite the high prevalence of diabetes in the world, its possible effects throughut pregnancy on neonatal auditory nervous system development are still unknown. In the present research, maternal diabetes’ impact on the M2 and Adrenergicα2 receptors expression in the inferior colliculus (IC) of male newborn rats was investigated. Main MethodsFemale rats were grouped into three: sham, insulin-treated diabetic, and diabetic. Diabetes was induced through streptozotocin (STZ) injection as one dose intraperitoneally (65 mg/kg). After mating and delivery, male rats were euthanized on P0, P7, and P14. Immunohistochemistry (IHC) was used to study the distribution pattern of receptors. Key FindingsThe present study indicated that the expression of M2 receptors in the diabetic group was significantly increased in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest M2 expression was for the diabetic group on P14 and the lowest one was for the sham group on P0. The Adrenergicα2a receptors expression in the diabetic group was significantly reduced in pairwise comparisons in the sham and diabetic treated with insulin groups (P < 0.001, each). The highest Adrenergicα2a expression was for the sham group on P14 and the lowest one was for the diabetic group on P0. There was no significant difference between the sham and insulin groups regarding all receptors expression. SignificanceThis study demonstrated a time-dependent significant decrease in Adrenergicα2a but a time-dependent significant increase in M2 receptors expression.

Gestational exposure to bisphenol A induces region-specific changes in brain metabolomic fingerprints in sheep.

Fetal brain development depends on maternofetal thyroid function. In rodents and sheep, perinatal BPA exposure is associated with maternal and/or fetal thyroid disruption and alterations in central nervous system development as demonstrated by metabolic modulations in the encephala of mice. We hypothesized that a gestational exposure to a low dose of BPA affects maternofetal thyroid function and fetal brain development in a region-specific manner. Pregnant ewes, a relevant model for human thyroid and brain development, were exposed to BPA (5µg/kg bw/d, sc). The thyroid status of ewes during gestation and term fetuses at delivery was monitored. Fetal brain development was assessed by metabolic fingerprints at birth in 10 areas followed by metabolic network-based analysis. BPA treatment was associated with a significant time-dependent decrease in maternal TT4 serum concentrations. For 8 fetal brain regions, statistical models allowed discriminating BPA-treated from control lambs. Metabolic network computational analysis revealed that prenatal exposure to BPA modulated several metabolic pathways, in particular excitatory and inhibitory amino-acid, cholinergic, energy and lipid homeostasis pathways. These pathways might contribute to BPA-related neurobehavioral and cognitive disorders. Discrimination was particularly clear for the dorsal hippocampus, the cerebellar vermis, the dorsal hypothalamus, the caudate nucleus and the lateral part of the frontal cortex. Compared with previous results in rodents, the use of a larger animal model allowed to examine specific brain areas, and generate evidence of the distinct region-specific effects of fetal BPA exposure on the brain metabolome. These modifications occur concomitantly to subtle maternal thyroid function alteration. The functional link between such moderate thyroid changes and fetal brain metabolomic fingerprints remains to be determined as well as the potential implication of other modes of action triggered by BPA such as estrogenic ones. Our results pave the ways for new scientific strategies aiming at linking environmental endocrine disruption and altered neurodevelopment.

Histological endpoints and oxidative stress transcriptional responses in the Mediterranean mussel Mytilus galloprovincialis exposed to realistic doses of salicylic acid

Despite the availability of analytic data, little is known about the toxicity of salicylic acid (SA) on aquatic non-target organisms. The present study aimed at evaluating the impact of SA through a short-term exposure of the Mediterranean mussel Mytilus galloprovincialis to five environmentally relevant concentrations of SA. A set of suitable biomarkers was applied at selected time-points on mussel digestive glands, including histological observations and expression of oxidative stress related genes. The obtained results showed a conspicuous hemocytic infiltration among mussel digestive tubules, as confirmed also by a flow cytometric approach that revealed an increase of halinocytes and granulocytes. Interestingly, a significant dose and time dependent decrease in the expression levels of oxidative stress related genes was found in mussels exposed to SA except for the glutathione S-transferase gene that was significantly up-regulated in a time-dependent manner confirming its important role against oxidant species and in the metabolism of pharmaceuticals.

GnRH agonist treatment regulates IL-6 and IL-11 expression in endometrial stromal cells for patients with HRT regiment in frozen embryo transfer cycles

To evaluate the effect of gonadotropin-releasing hormone agonist (GnRHa) pretreatment time on clinical outcomes of patients who underwent endometrial preparation in HRT cycles and the molecular mechanism in frozen-thawed embryo transfer (FET) cycles, we retrospectively chose 1143 cycles and separated four groups. Endometrial tissues were collected from 44 patients who were cancelled on the day of embryo transfer (there were 10 patients refused to collect endometrium) and were tested for endometrial receptivity marker mRNA and miR-124-3p expression. Furthermore, endometrial stromal cells (ESCs) were transfected to investigate the molecular mechanism. The clinical pregnancy rate and live birth rate were significantly high in group B. The endometrial expression of the IL-6 and IL-11 mRNAs was significantly increased in groups with GnRHa pretreatment compared with group A without the GnRHa pretreatment. Similar results were obtained for the endometrial receptivity markers LIF and integrin αvβ3. The groups treated with GnRHa exhibited a progressive and significant time-dependent decrease in the IL-6 and IL-11 mRNA. In contrast, the levels of LIF and integrin αvβ3 expression remained unaltered among group B-D. In addition, transfection of ESCs with miR-124-3p mimics significantly reduced levels of the IL-6 and IL-11 mRNAs and proteins. The luciferase report assay demonstrated that IL-6 and IL-11 is a target gene of miR-124-3p. The results showed that ultra-long GnRHa administration can improve outcomes, especially after 3 cycles of GnRHa pretreatment, and endometrial receptivity through IL-6 and IL-11 expression levels of ESC regulated by the miR-124-3p for patients with HRT, who underwent FET cycles.

Modification of physical and functional characteristics of chitin extracted from microwave-treated Nelumbo nucifera rhizome flour

Chitin, a cell wall polysaccharide, extracted from Nelumbo nucifera rhizome (NNR), was subjected to microwave treatment to modify its physical and functional characteristics. The NNR flour was irradiated at different levels of the microwave treatment period (1, 2, 3, 4, and 5 min). Chitin was extracted from the native and microwave-treated samples and analyzed for physical and functional characteristics. The microwave treatment resulted in some variations in the extract yield, structure, morphology, and composition of chitin that were directly correlated with its functional properties. Regression analysis of the data showed a significant ( p &lt; 0.05) time-dependent linear decrease in extract yield, polynomial decrease in water-holding and swelling capacities, an exponential increase in oil holding, and an exponential decrease in iron-binding capacity of chitin extracted from microwave-treated flour. These variations in the studied functional properties may be due to microwave-induced hydrolytic degradation of chitin, structural rearrangements, and exposure of some lipophilic functional groups on the surface of chitin. The data would be a valuable contribution to the literature regarding microwave-induced modification in physical and functional characteristics of chitin present in N. nucifera rhizome and other plant-based biomaterials of industrial importance.

BEHAVIOURAL RESPONSES OF AFRICAN CATFISH ( Clarias gariepinus BURCHELL, 1822) JUVENILES EXPOSED TO ACUTE CONCENTRATIONS OF BUTACHLOR (HERBICIDE)

This study examined the behavioral changes induced by butachlor to the juveniles of Clarias gariepinus. The experiment consists of five treatments (0.6, 0.7, 0.8, 0.9 and 1.0 mg/l) and a control. Ten fishes were allotted in each test tank in duplicates. Observations on behavioral responses were made at 0, 12, 24, 48, 72 and 96 hours post-exposure. The opercular movement and tail fin beat rates were observed as counts per minute using a stopwatch. The behavioral patterns of the fish in the control group were normal, whereas in the exposed groups the fish tend to lose equilibrium and swim erratically with vigorous jerky movements. At the 12th and 24th hours the fish in the exposed groups showed hyper-active movement, but became hypoactive at the 48th hour. The mean values of the tail fin beat of the exposed groups were significantly higher (p&lt;0.05) than that of the control at the 12th hour. At the 24th and 48th hour post-exposure the exposed groups showed significant (p&lt;0.05) time-dependent decrease compared to the control. The tail fin beat became significantly higher (P&lt;0.05) in the control group from 72nd hours onward. The decrease of tail fin beats at the 72nd and 96th hours were dose-dependent similar observations were also recorded in the opercular ventilation. At the 12th hour the opercular ventilation of the exposed fish was significantly higher (p&lt;0.05) than the control whereas at the 24th and 48th hours, the opercular ventilation of the exposed groups showed a significant decrease (p&lt;0.05) compared to the control.

Improved Cardiac Function and Attenuated Inflammatory Response by Additional Administration of Tirofiban during PCI for ST-Segment Elevation Myocardial Infarction Patients.

ST-segment elevation myocardial infarction (STEMI) is one of the acute coronary syndromes, and it is the main cause of cardiac death worldwide. The purpose of this study was to investigate whether tirofiban improves cardiac function and attenuates inflammatory response in STEMI patients undergoing percutaneous coronary intervention (PCI). From May 2016 to May 2019, a total of 124 patients who admitted into our hospital due to STEMI fulfilled inclusion and exclusion criteria and were randomly assigned to PCI + tirofiban and PCI groups, 62 cases per groups. Intravenous administration of 10 μg kg−1 min−1 tirofiban was performed 30 min prior to PCI. During PCI, tirofiban infusion through a micropump with 0.15 μg kg−1 min−1 lasted for 48 h. It was found that the PCI + tirofiban group was significantly different from the PCI group in total corrected TIMI frame count (CTFC) after PCI (15.88 ± 5.11 vs. 22.47 ± 6.26, P < 0.001). At day 7 and day 30 post-PCI, a significant time-dependent decrease in the levels of brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and creatine kinase isoenzyme (CK-MB) in both groups was observed after PCI (P < 0.001). More importantly, the patients in the PCI + tirofiban group had much lower levels of BNP, cTnI, and CK-MB compared with those in the PCI group at days 7 and 30 post-PCI (P < 0.001). At day 7 following PCI, the left ventricular ejection fraction (LVEF) was statistically higher in the PCI + tirofiban group than in the PCI group (P < 0.05). At day 30 post-PCI, increased LVEF concomitant with reduced left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) was observed in the PCI + tirofiban group compared with the PCI group. At day 7 and day 30 post-PCI, both groups displayed a time-dependent decline in the levels of C reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and procalcitonin (PCT) after PCI (P < 0.05). Additionally, the patients in the PCI + tirofiban group had lower levels of CRP, TNF-α, IL-6, and PCT compared with those in the PCI group at days 7 and 30 post-PCI (P < 0.05). All patients in the PCI + tirofiban and PCI groups were followed up for 12 months by outpatient or telephone after discharge. There were fewer patients with LVEF < 50% in the PCI + tirofiban group than the PCI group (P=0.044). Furthermore, it was found that the incidence rate of major adverse cardiovascular events (MACEs) in the PCI + tirofiban group was evidently lower than that in the PCI group (12.90% vs. 29.03%, P=0.028). Taken together, our data suggest that additional administration of tirofiban could improve cardiac function and attenuate inflammatory response in STEMI patients undergoing PCI, which is worthy of promotion in clinic.

Anti-nociceptive and anti-inflammatory effects of the hydroethanolic extract of a polyherbal preparation (Cov-Pla 2) in laboratory animals

Symptoms of Coronavirus Disease-2019 include pulmonary hyper-inflammation; managing local and systemic inflammatory responses may be key in treatment. This study evaluated the anti-inflammatory, analgesic and antipyretic effects of a mixture (Cov-Pla 2) containing five medicinal plants in laboratory animals. The antinociceptive activity of Cov-Pla 2 was evaluated using acetic acid-induced writhing, Brewer’s Yeast Pyrexia test in rats and hot plate tests in mice. The egg albumin-induced rat paw oedema test was employed to evaluate the extract’s anti-inflammatory activity. The extract produced a dose-dependent (125-500 mg/kg, p.o.) inhibition of pain response elicited by acetic acid, compared to normal saline and increased reaction latency in the hot plate test. The antiinflammatory test showed a significant (P&lt;0.05) reduction in paw size diameter at 125 mg/kg from 2 hours, compared to control. In the antipyretic test, the extract produced a significant (P&lt;0.05) time-dependent decrease in rectal temperature at 125 mg/kg after 2 and 3 hours and at 250 and 500 mg/kg after 3 hours, compared to normal saline. The extract did not produce mortality up to 5000 mg/kg per oral. The results indicated that the extract possesses antinociceptive and anti-inflammatory properties, which support its recommendation for trials in the treatment of symptoms associated with COVID-19.&#x0D; Keywords: COVID-19; Inflammation; Nociception; Polyherbal; SARS-CoV-2

Microwave-Induced Modification of Physical and Functional Characteristics and Antioxidant Potential of Alkali-Soluble Cell Wall Polysaccharides of Nelumbo nucifera Rhizome

The alkali-soluble cell wall polysaccharides (CWPs), extracted from Nelumbo nucifera rhizome flour (NNRF), were treated with microwave radiation to modify their physical characteristics, functional properties, and antioxidant potential. The NNRF was treated at different levels of microwave treatment time (1, 2, 3, 4 and 5 min) using the low-medium intensity (200 W). The cell wall was isolated and CWPs were extracted in 10% KOH solution followed by their physical, functional, and antioxidant characterization. Microwave treatment resulted in the morphological, structural and compositional modifications in CWPs that were directly correlated with their functional properties and antioxidant potential. A significant (p < 0.05) time-dependent exponential decrease in extract yield, exponential increase in water holding, oil holding, and swelling capacities, a polynomial increase in iron-binding capacity, and a linear increase in antioxidant properties including Trolox equivalent total antioxidant activity, ferrous reducing power, and free radical scavenging capacity of microwave-treated CWPs was observed. The increase in the studied functional and antioxidant potential of the treated samples may be due microwave-induced exposure of hydroxyl groups and uronic acid residues in CWPs. The data would be a valuable contribution to the literature regarding microwave-induced modification in physical, functional and antioxidant properties of CWPs of N. nucifera rhizome.