Human Plasma Research Articles

Sex ratios of olive ridley sea turtles in the North Pacific high seas: implications for climate change research

Size-class distributions and sex ratio data provide critical information to assess the demography and reproductive potential of animal populations, such as sea turtles. Sea turtle sex is determined by incubation temperature, whereby warmer temperatures during a certain period of embryonic development produce more female hatchlings. Whereas hatchling sex ratios have been well-studied, sex ratios of sea turtle foraging aggregations are less known for most populations. Here we report on sex ratios of immature and mature olive ridley sea turtles Lepidochelys olivacea in the Eastern Tropical Pacific (ETP) and Central North Pacific (CNP) based on blood plasma hormone analysis, refined with Bayesian modeling, or gonad examination. Our findings established that (1) the commercial enzyme-linked immunosorbent assay used in the present study was appropriate to analyze testosterone concentration in olive ridley blood plasma to determine foraging ground sex ratios (via a Bayesian model); (2) size-at-maturity is generally larger in males than females in the ETP; (3) the overall sex ratio among all turtles was 1.2F:1.0M; and (4) the sex ratio of smaller-sized immature turtles from both study regions was female-biased (ETP, 1.6F:1.0M and CNP, 2.1F:1.0M). These are the first sex ratio estimates for olive ridleys foraging in the high seas of the North Pacific Ocean. The data can inform population models for species conservation, particularly those that contribute to the development of conservation plans that consider climate change projections.

Examining Whole Blood, Total and Free Plasma Tacrolimus in Elderly Kidney Transplant Recipients

Background: Therapeutic monitoring is routinely performed to ensure tacrolimus whole-blood concentrations fall within a predefined target. Despite this, patients still experience inefficacy and toxicity that could be related to variability in free (unbound) tacrolimus exposure. Therefore, the aim of this study was to compare tacrolimus-free plasma (Cu), total plasma (Cp), and whole-blood (Cwb) concentrations in adult kidney transplant recipients and to characterize tacrolimus disposition across different matrices. Methods: Twelve-hour concentration–time profiling was performed in 15 recipients, allowing simultaneous measurement of Cu, Cp, and Cwb. Pharmacokinetic parameters were estimated using noncompartmental analysis. The relationship between Cwb and Cp were examined using a capacity-limited binding model, incorporating the hematocrit fraction (f HCT) to estimate maximum binding concentration (B max) and dissociation constant (K d ). The relationship between Cp and Cu was evaluated using a linear binding model to estimate the nonspecific binding parameter (N plasma ). Nonlinear regression analysis was used to obtain estimates of B max, K d , and N plasma . Results: A total of 195 paired Cwb, Cp, and Cu values were collected. The median ratios of Cwb:Cp, Cp:Cu, and Cwb:Cu were 9:1, 20:1, and 138:1, respectively. Variability in free plasma exposure was large; free trough values ranged from 8 to 51 ng/L and free area-under-the-concentration–time-curve values ranged from 424 to 7160 ng·h/L. Median (range) estimates of B max, K d , and N plasma were 90.4 µg/L (22.4–752.5 µg/L), 2.36 µg/L (0–69.2 µg/L), and 0.05 (0.035–0.085), respectively. The interindividual variability (CV%) in binding parameters was considerable (B max 117.2%; N plasma 32.5%). Conclusions: Large variability was observed in tacrolimus-free plasma exposure and binding parameters. Future research to characterize the relationship between tacrolimus Cu and patient outcomes may be of benefit.

Immunological quality of colostrum and specific antibodies against enteropathogens in the colostrum and transition milk of crossbred Gir × Holstein cows.

Colostrum management is crucial for enhancing the immune response against enteropathogens and the survival of dairy calves during the first few weeks of life. However, few physiological studies have investigated the dynamics of general and specific immunoglobulin G (IgG) content in cow milk during early lactation stages, particularly in that of crossbred Gir × Holstein dairy cows, the most predominant dairy cattle population in tropical countries, such as Brazil. Therefore, this study evaluated the effects of parity and milking order on the volume and quality of colostrum, transition milk, and mature milk in crossbred Gir × Holstein cows using three traditional on-farm tests. The dynamics of IgG in the mammary secretions and the specific antibody levels against enteropathogens were also determined using sandwich enzyme-linked immunosorbent assay (ELISA) during the early stages of lactation. Fifty healthy Gir × Holstein cows were divided into two groups based on parity number, i.e., primiparous (n = 18) and multiparous (n = 33). They were monitored from the first to the 43rd milking. The colostrum volume and quality were evaluated using a colostrometer, Brix refractometer, and Colostro Balls after the first milking, in addition to the colostral IgG levels measured using sandwich ELISA as a reference standard. On-farm tests showed that the colostrum samples obtained from Gir × Holstein cows exhibited an optimal colostrum quality based on the literature criteria, regardless of parity number; however, the IgG mass was higher in the colostrum of multiparous (201 ± 67.03g) cows than in that of primiparous (144 ± 32.40g) cows. The volume and composition of transition and whole milk were also assessed at the second to ninth, 11th, 13th, 15th, 29th, and 43rd milkings. Multiparous cows produced higher volumes of transition milk than primiparous cows. In addition, multiparous cows exhibited a higher total solids percentage in their postpartum mammary secretions than primiparous cows. A higher percentage of inhibition of specific antibodies against Escherichia coli K99 was observed in the blood serum of multiparous cows than in that of primiparous cows. The volume and composition of mammary secretions changed over time; milk production increased, whereas total solids, total IgG, and specific antibody levels against most enteropathogens decreased, regardless of parity. Additionally, an association between parity and time was observed with respect to milk yield, the Brix score (%), and specific antibody levels against the Clostridium perfringens alpha toxin in mammary sections and against coronavirus and rotavirus in blood samples. This association indicated higher values in multiparous cattle than in primiparous cattle at specific time points. In conclusion, this study reveals postpartum time-dependent changes in the physiological and immunological components in the mammary secretions and blood of crossbred Gir × Holstein cows from the first to the 43rd milking. These results will contribute to the development of future research in Gir × Holstein-specific neonatology, which is genetically adapted to tropical and subtropical countries.

Efficacy of compound sodium acetate Ringer's solution in early fluid resuscitation for children with septic shock: a preliminary retrospective cohort study.

The effectiveness of acetated Ringer's solution in pediatric shock has received little attention. This study aimed to assess the clinical outcomes of using compound sodium acetate Ringer's solution (AR) for fluid resuscitation in children with septic shock. We retrospectively analyzed the clinical data of children with septic shock admitted to the pediatric intensive care unit of the Affiliated Hospital of Southwest Medical University from December 2019 to January 2023. Based on the resuscitation fluid administered, the participants were categorized into the compound AR and normal saline (NS) groups. We compared blood circulation conditions, internal environment parameters (arterial blood pH, lactic acid, serum sodium, chloride, calcium, magnesium, potassium, and blood glucose), and 28-day clinical outcomes between the two groups. This study included 40 children, with 13 and 27 in the compound AR and NS groups, respectively. The two groups showed no significant differences in sex, age, body weight, body mass index, primary inflammation level, or Pediatric Sequential Organ Failure Assessment on admission. Similarly, no significant difference was observed in resuscitation fluid volume administered during the first hour (compound AR group: 250.00 mL [100.00, 390.00]; NS group: 250.00 mL [100.00, 500.00]). The total amount of crystalloid and colloid fluids administered within 24h, vasoactive drug use, and blood pressure recovery post-resuscitation did not significantly differ between the groups. However, at 6h post-resuscitation, the compound AR had considerably lower lactate level than the NS group (1.12 vs. 2.20 mmol/L). There were no significant differences in arterial blood pH, serum sodium, chloride, calcium, magnesium, potassium, and blood glucose levels between the groups. After treatment, in the compound AR group, 3 patients died, 2 improved, and 8 were cured. In the NS group, 7 patients died, 8 improved, and 12 were cured. The 28-day treatment outcomes (mortality rate, improvement rate, cure rate, or side effects) showed no significant differences between the groups. Compound AR was as effective as NS as a resuscitation fluid in pediatric septic shock, demonstrating similar intravascular volume restoration and hemodynamic stability maintenance. However, it caused a faster decline in arterial lactate levels without obvious side effects.

Host-Guest Adduct as a Stimuli-Responsive Prodrug: Enzyme-Triggered Self-Assembly Process of a Short Peptide Within Mitochondria to Induce Cell Apoptosis.

To address the issue of nonspecific biodistribution of a chemotherapeutic drug, stable [2]pseudorotaxane complexes (PK@CAOPP and PR@CAOPP) are used to demonstrate a proof of concept. Cationic -PPh3 + moiety in CAOPP allows specific localization of the PK@CAOPP/ PR@CAOPP in the mitochondrial membrane (MM). Electrostatic interaction between the cationic LysinePK or ArgininePR moiety and the negatively charged phosphoesterCAOPP functionality in CAOPP favours strong adduct formation. The ALP-induced hydrolytic cleavage of the phosphoester moiety in cancer cells triggers dephosphorylation and releases PK/ PR moiety from PK@CAOPP/PR@CAOPP. PK or PR, derived from the Phe-Phe dipeptide, formed fibril-like molecular aggregates in the MM to induce dysfunction, depolarization, ROS generation and apoptotic MCF7 cell death. Such phenomena were not observed in ALP-negative HEK293 normal cells. These propositions were confirmed through control studies using NBDK and PE, other guest molecules. Smaller size and inclusion of the short peptides (PK or PR) within the hydrophobic interior of CAOPP, were attributed to their stability in blood serum. Thus, we have demonstrated the use of supramolecular adducts as a potential therapeutic option for treating cancer cells without affecting healthy cells. The efficacy was also established with an in-vivo MCF7 tumour xenograft model using Balb/c nude mice.

Effect of Chronic Consumption of Fluoridated Water on Sciatic Nerve Conduction Velocity in Male Wistar Rats.

The long-term effect of fluoridated water consumption during development on the velocity of nerve impulse conduction in the sciatic nerve of rats was assessed. Thirty male Wistar rats, 21 days old, were randomly assigned to five groups. Three groups were given fluoridated water ad libitum (as the only source) at different concentrations (10, 100, and 150 ppm), designated as groups F10, F100, and F150, respectively. The study included a control group (C) that received fluoridated water at the maximum level established by the World Health Organization (1.5 ppm of fluorides) and another group that received deionized water (DW). The animals were treated until they reached 90 days of age. Electrophysiological recordings were performed on the rats' sciatic nerves to determine nerve conduction velocity, and blood plasma was extracted for fluoride concentration analysis. The study found that the F150 group had a lower nerve impulse conduction velocity in the sciatic nerve compared to the C group (P = 0.0015). Additionally, there was a negative correlation between the concentration of fluorides in plasma and the nerve conduction velocity (r = -0.5132, P = 0.0037). These findings indicate that chronic consumption of high concentrations of fluoride leads to a decrease in nerve conduction velocity. This, in conjunction with potential alterations in the central nervous system, may explain the deficits in learning and memory tests that have been documented in numerous studies evaluating individuals exposed to fluoride consumption. These results provide valuable information for understanding the effects and action mechanisms of fluoride in exposed individuals.

Ameliorative effect of rutecarpine supplementation against cisplatin-induced nephrotoxicity in rats via inhibition of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B.

Cisplatin, the pioneering heavy metal compound, stands out as a potent drug for the treatment of various solid tumors. However, its clinical utility is hampered by notable toxicity and adverse effects, particularly nephrotoxicity. The potency of rutecarpine, a phytochemical, in mitigating cisplatin-induced nephrotoxicity was assessed in the present study. In this experimental setup, healthy male Wistar rats were grouped into four and Group I rats served as the control group, receiving only vehicle control. Group II rats were subjected to cisplatin treatment alone, administered intraperitoneally at a dosage of 7mg/kg body weight on the 19th, 20th, and 21st days. Group III and IV rats were orally administered with rutecarpine at doses of 10 and 20mg/kg body weight, respectively, starting from Day 1 and continuing daily for 21 days. Additionally, they were injected intraperitoneally with cisplatin at the same dosage and schedule as Group II. Relative kidney weight and renal biochemical markers blood urea nitrogen, lactate dehydrogenase, serum urea, and creatinine were measured to assess rutecarpine inhibitory potency against cisplatin toxicity. Markers of oxidative damage and antioxidants levels were quantified in the ruteacarpine- and cisplatin-treated rats. The study investigated the anti-inflammatory property of rutecarpine in cisplatin-induced nephrotoxicity by analyzing inflammatory cytokines. Renal tissue levels of monocyte chemoattractant protein-1, intercellular adhesion molecule-1, high-mobility group box 1, and nuclear factor kappa B, key markers of nephrotoxicity, were quantified to assess rutecarpine's potential to mitigate cisplatin-triggered damage. Histopathological examinations were performed to confirm the impact of rutecarpine against cisplatin-induced nephrotoxicity. Treatment with rutecarpine notably reduced renal biochemical markers, prevented renal edema, and attenuated oxidative stress-induced damage in cisplatin-treated rats. Both inflammatory and nephrotoxicity markers showed significant decreases in rats treated with rutecarpine along with cisplatin. Histological analysis affirmed that rutecarpine pretreatment effectively prevented cisplatin-induced nephrotoxicity. The study findings demonstrate that rutecarpine ameliorates cisplatin-triggered nephrotoxicity through its antioxidant and anti-inflammatory properties, suggesting that rutecarpine supplementation alongside cisplatin treatment could potentially reduce nephrotoxicity in cancer patients.

IgA monoclonal gammopathies are accompanied by higher total TGF-β1 levels than IgG or IgM monoclonal gammopathies.

The progression of monoclonal gammopathies is affected by a range of factors, including the microenvironment surrounding plasma cells. It is recognized that TGF-β1 plays a distinct role in stimulating IgA production. Hence, this study aims to investigate whether individuals with serum IgA monoclonal immunoglobulins (paraproteins) exhibit elevated total TGF-β1 levels compared to those with IgG or IgM paraproteins. To achieve this goal, individuals with a positive laboratory finding of monoclonal gammopathy were segregated according to the paraprotein class as well as according to the type of the light chain. Total TGF-β1 levels were assessed in blood serum samples containing IgG (n = 50), IgA (n = 46), and IgM (n = 31) paraproteins. Elevated level of TGF-β1 was confirmed in sera with IgA paraproteins (median 25.8 ng/mL; interquartile range IQR: 19.0-33.7) compared to those having IgG (median: 18.2 ng/mL; IQR: 14.3-22.1; p < 0.001) or IgM paraproteins (21.5 ng/mL; IQR: 15.0-27.4; p = 0.043). Also, a higher TGF-β1 level was detected in sera with IgMλ than those with IgMκ paraproteins (p = 0.043). This research affirms the role of TGF-β1 in the pathophysiology of IgA monoclonal gammopathies and the potential switch towards the IgA isotype, known for a less favourable prognosis.

Predictive value of pre-treatment circulating tumor DNA genomic landscape in patients with relapsed/refractory multiple myeloma undergoing anti-BCMA CAR-T therapy: Insights from tumor cells and T cells.

B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM. Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells. In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow (P=0.013), lower percentages of CAR-T cells in the peripheral blood at peak (P=0.037), and higher percentages of CD8+ T cells (P=0.034). Furthermore, there is a substantial correlation between high ctDNA level (>143ng/mL) and shorter progression-free survival (PFS) (P=0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143ng/mL), MM-driven high-risk mutations (including IGLL5 [P=0.004], IRF4 [P=0.024], and CREBBP [P=0.041]), number of multisite mutations, and resistance-related mutation (ERBB4, P=0.040) were independent risk factors for PFS. Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy. Chinese Clinical Trial Registry (ChiCTR2100046474) and National Clinical Trial (NCT04670055, NCT05430945).

Evaluation of Ethanolic Extract of Red Seaweed (Gracilariopsis lemaneiformis) on Growth and Haematological Parameters of Nile Tilapia (Oreochromis niloticus)

ABSTRACTSeaweed is multicellular marine macroalgae that enhances the immunity of aquatic organisms. The study was designed to assess the ethanolic extract (EtOH) extracted from red seaweed (Gracilariopsis lemaneiformis) on Nile tilapia (Oreochromis niloticus) to evaluate growth, immunity and haematological parameters. The EtOH was applied with fish feed in four treatments such as T1‐control (0% EtOH), T2 (5% w/v EtOH), T3 (10% w/v EtOH) and T4 (15% w/v EtOH) each with three replicates. The initial average weight of the fish was 17.53 ± 2.1 g. Results showed that the growth increased gradually with the percentage of red seaweed extract, whereas the mean weight gain was found significantly higher in T4 (51.5 ± 4.2) than in the control. The specific growth rate (%) and survival rate (%) were found higher in T4 at the lowest FCR compared to other treatments (p &lt; 0.05). The blood haemoglobin level of Nile tilapia was higher in T4 (11.5 g/dL) and lowest recorded in T1 (7.5 g/dL). However, the level of blood glucose interacted inversely with blood haemoglobin. The plasma protein level was also varied among the treatments (p &gt; 0.05). The blood parameters, refractive index (RI) and spleen somatic index (SSI) were significantly different among the treatments. The RI of blood plasma and SSI were found to be better in T4 treatment. The research indicated that red seaweed extracts significantly enhanced the growth and boosted the immunity level of Nile tilapia.

Utility of Gold/Multiwalled Carbon Nanocomposite for Electrochemical Determination of Omarigliptin in Tablets and Human Plasma

Abstract An innovative voltammetric sensor was developed to estimate omarigliptin, a novel long-acting anti-diabetic drug. The sensor utilized a carbon paste electrode enhanced with a nanocomposite of carbon nanotubes and electrodeposited gold nanoparticles. The modified electrode was characterized using scanning electron microscopy and electrochemical impedance spectroscopy. The modification significantly improved the electrode's sensitivity and electrochemical efficiency and decreased its electron transfer resistance. The surface area of the modified electrode increased by about 2.8-fold compared to the bare electrode. Omarigliptin's oxidation behavior on the modified electrode was pH-dependent and irreversible, resulting in a peak current 4 times higher than the unmodified electrode. The modified electrode revealed good reproducibility, reusability, and stability. It allows for sensitive voltammetric analysis of omarigliptin over a linear range of 0.4–27 µM (LOD=0.12 µM) and good applicability in tablets and plasma. The recovery percentages are 98.47–101.27% in tablets and 95.86–105.02% in plasma. The modified electrode exhibits good selectivity towards OMR without interference from tablet excipients, endogenous plasma components, and co-administered drugs. The comparison with the reported methods reveals the superiority of the proposed method in terms of sensitivity, selectivity, applicability, and eco-friendliness. Finally, the proposed method demonstrates excellent environmental profiles based on recent assessment metrics.

Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.

Our previous work established a role for actin associated myosin motor proteins MYH9 and MYH10 in the trafficking of thick ascending limb (TAL) specific cargoes, uromodulin (UMOD) and Na+K+2Cl- cotransporter (NKCC2). Here, we have generated a TAL-specific Myh9&10 conditional knockout (Myh9&10 TAL-cKO) mouse model to determine the cell autonomous roles for MYH9&10 proteins in TAL cargo transport and to understand the consequence of TAL dysfunction in the adult kidney. Myh9&10 TAL-cKO mice develop progressive kidney disease with pathological tubular injury confirmed by histological changes, tubular injury markers, upregulation of ER stress/unfolded protein response pathway, and higher blood urea nitrogen and serum creatinine. However, male mice survive twice as long as female mice. We determined that the sexual dimorphism in morbidity is due to adaptation of the distal nephron and the collecting ducts in response to TAL dysfunction and significantly lower NKCC2 expression. We demonstrate that this triggers a compensatory mechanism involving sex-specific cellular adaptation within the distal tubules and collecting ducts to boost sodium reabsorption. While both sexes overcompensate by activating ENaC expression in the medullary collecting ducts resulting in hypernatremia, this is subdued in male Myh9&10 TAL-cKO mice as they initially promote higher sodium chloride cotransporter (NCC) expression within the distal nephron. Our results indicate that compromised TAL function results in maladaptation of medullary collecting duct cells, which acquire cortical-like properties, including ENaC expression. This work further confirms a cell autonomous role for myosin motor proteins MYH9&10 in the maintenance of NKCC2 expression in the TAL and uncover adaptive mechanisms of the distal nephron and the collecting duct segments in response to TAL dysfunction.

The effects of SOD Melon Gliadin as an Antioxidant on VEGF and TGF β blood serum and vitreoretina in hyperglycemia rat model a literature review

Diabetes Mellitus is a chronic metabolic disorder characterized by hyperglycemia resulting from impaired insulin secretion, action, or both. Persistent hyperglycemia can lead to organ damage, including ocular complications such as diabetic retinopathy. Diabetic retinopathy is a primary cause of preventable blindness and can become vision-threatening if complications are persistent. Over one-third of individuals with diabetes exhibit signs of diabetic retinopathy, and among them, approximately one-third experience vision-threatening diabetic retinopathy (VTDR), defined as severe non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or the presence of diabetic macular edema (DME). Diabetic retinopathy triggers the production of reactive oxygen species (ROS). Excessive accumulation of ROS can damage tissues surrounding retinal blood vessels, leading to oxidative stress that compromises the blood-retina barrier (BRB). Vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) are two markers that indicate retinal dysfunction. Cells possess an intrinsic defense system against ROS, comprising antioxidants such as superoxide dismutase (SOD), glutathione reductase, glutathione peroxidase, and catalase. SOD melon gliadin (Glisodin®) is a potent antioxidant that elevates endogenous SOD levels, reduces ROS, and protects retinal tissues from damage and cell death. Research on SOD melon gliadin (Glisodin®) shows its potential as an antioxidant for preventing diabetic complications in the retina, specifically diabetic retinopathy.

Circulating microRNAs associated with bronchodilator response in childhood asthma

BackgroundBronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology.ObjectiveThe purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation.MethodsWe used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into the highest and lowest bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N = 277) vs. low (N = 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed.ResultsWe identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR = 2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways.ConclusionMiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients.Trial registrationLOCCS cohort [ClinicalTrials.gov number NCT00156819, Registration date 20050912], GACRS cohort [ClinicalTrials.gov number NCT00021840].

Metabolomic profiling of human feces and plasma from extrauterine growth restriction infants.

Extrauterine growth restriction (EUGR) affects a substantial proportion of preterm infants and may influence both short-term complications and long-term sequelae. While many preterm infants with EUGR are secondary to small for gestational age (SGA) or very low birth weight (VLBW), a subset of EUGR infants do not exhibit these conditions. The purpose of this study is to investigate the metabolic profiles and biomarkers of EUGR infants in the absence of SGA and VLBW. A total of 100 feces (n = 50) and plasma samples (n = 50) were collected from participants categorized as either EUGR (EUGR group) or non-EUGR (NonEUGR group) in the absence of SGA and VLBW. Metabolites were characterized via UPLC-MS/MS using the Discovery HD4® platform. Data normalization, partial least squares discriminant analysis (PLSDA), and KEGG enrichment analysis of metabolite profiles were performed using the MetaboAnalyst 6.0. The clinical characteristics of preterm infants differed significantly between the EUGR and NonEUGR groups at discharge, including length of stay, weight Z-score, weight, height Z-score, height, head circumference, and fat-free mass. The PLSDA model exhibited clustering within groups and separation between groups. A total of 58 and 71 differential metabolites were identified in feces and plasma samples, respectively. They were involved in pathways such as caffeine, galactose, glutathione, cysteine, and methionine metabolisms. In the feces sample, 1-palmitoyl-galactosylglycerol exhibited a significant negative correlation with the growth characteristics of preterm infants, while 1-palmitoyl-2-palmitoleoyl-GPC displayed the opposite pattern. In plasma samples, androsterone glucuronide displayed a significant positive correlation with the growth characteristics of preterm infants, whereas 2-methoxyhydroquinone sulfate generated an opposite pattern. Moreover, 2-oleoylglycerol and sphinganine-1-phosphate exhibited the highest area under the curve in feces and plasma samples, respectively, according to diagnostic ROC curves. Preterm infants with EUGR, in the absence of SGA and VLBW, exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol may hold promise as diagnostic markers for EUGR in the absence of SGA and VLBW. The objective of this study is to identify the differential metabolites in preterm infants with extrauterine growth restriction (EUGR) in the absence of small for gestational age (SGA) or very low birth weight (VLBW). Preterm infants with EUGR without SGA and VLBW exhibit specific clinical characteristics and metabolomic profiles. Sphinganine-1-phosphate and 2-oleoylglycerol emerged as potential diagnostic biomarkers for EUGR. This study enhances our understanding of the metabolomic profile in preterm infants with EUGR without SGA or VLBW. Our findings will offer valuable evidence for improving nutritional management and shedding light on the associated pathophysiological mechanisms of EUGR.

Membrane-dependent reactions of blood coagulation: classical view and state-of-the-art concepts

The complex mechanism called hemostasis evolved in living organisms to prevent blood loss when a blood vessel is damaged. In this process, two closely interconnected systems are distinguished: platelet-vascular and plasmatic hemostasis. Plasmatic hemostasis is a system of proteolytic reactions, in which blood plasma proteins called coagulation factors are involved. A key feature of this system is the localization of enzymatic reactions on the surface of phospholipid membranes, which increases their rate by up to 5 orders of magnitude. This review describes the basic mechanisms of coagulation factors binding to phospholipid membranes, pathways for complex assembly and activation reactions, and discusses the role of membranes in this process, their composition and sources. The binding of coagulation factors to procoagulant membranes leads not only to the acceleration of coagulation reactions, but also to their selective localization in restricted areas and protection from being washed away by the flow. The efficiency of coagulation reactions is regulated by the composition of the outer layer of the membrane, primarily through a special mechanism of mitochondria-dependent necrotic platelet death.

Nutrition Modulation of Cardiotoxicity in Breast Cancer: A Scoping Review

Background/Objectives: Advancements in breast cancer therapeutics, such as anthracyclines, are improving cancer survival rates but can have side effects that limit their use. Cardiotoxicity, defined as damage to the heart caused by cancer therapeutics, is characterised by a significant reduction in left ventricular ejection fraction (LVEF) and symptoms of cardiac dysfunction. Multiple oral supplements exist with antioxidant and anti-inflammatory properties that have the potential to lower cardiotoxicity risk and ameliorate the complications associated with left ventricular dysfunction. In this review, we evaluate the current status of using nutritional interventions to modulate cardiotoxicity. Methods: We used specific keywords to search for articles that met our predetermined inclusion and exclusion criteria to review the evidence and provide insights for future research. Results: Seven studies were identified as eligible for this review: six focused on oral supplementation strategies in breast cancer patients undergoing chemotherapy, and one focused on nutritional counselling and adherence to the Mediterranean diet in breast cancer survivors’ post-treatment. There was a significantly attenuated reduction in LVEF in five studies that monitored cardiometabolic health, and there were significant improvements in blood serum levels of cardiac biomarkers across all studies. Conclusions: Current evidence suggests that appropriate nutritional interventions, alongside chemotherapy, can modulate the risk of cardiotoxic side effects. This highlights the potential of oral antioxidant supplementation and Mediterranean diet counselling to decrease tertiary cancer therapy costs associated with cardiovascular complications.

The Effect of the Acid-Base Imbalance on the Shape and Structure of Red Blood Cells

Red blood cells respond to fluctuations in blood plasma pH by changing the rate of biochemical and physical processes that affect the specific functions of individual cells. This study aimed to analyze the effect of pH changes on red blood cell morphology and structure. The findings revealed that an increase or decrease in pH above or below the physiological level of pH 7.4 results in the transformation of discocytes into echinocytes and causes significant alterations in the membrane, including its roughness, cytoskeleton structure, and the cell’s elastic modulus. Furthermore, the study shown a strong connection between critical acidosis and alkalosis with increased intracellular reactive oxygen species production.

Neutrophil Elastase, Neuron-Specific Enolase, and S100B Protein as Potential Markers of Long-Term Complications Caused by COVID-19 in Patients with Type 2 Diabetes Mellitus (T2DM) and Advanced Stage of Diabetic Nephropathy (NfT2DM)—Observational Studies

Despite numerous studies conducted by various research teams, predicting long-term outcomes (known as Post-COVID-19 Syndrome, PCS) that may result from Coronavirus Disease 2019 (COVID-19) remains challenging. PCS affects over a million people, primarily those with comorbid conditions. Therefore, it is crucial to undertake research aimed at developing a predictive model for early diagnosis of PCS, which in turn would enable faster preventive actions. The aim of this study was to assess the value of measuring and attempt a quantitative evaluation using Enzyme-Linked Immunosorbent Assay (ELISA) tests of three non-serum proteins, whose presence in the blood during COVID-19 was associated with severe disease progression: neutrophil elastase (NE), calcium-binding protein S100B, and neuron-specific enolase (NSE). The concentrations of these proteins were measured in blood serum samples collected before the COVID-19 pandemic from (1) patients with type 2 diabetes (T2DM); (2) advanced stage diabetic nephropathy (NfT2DM); (3) a healthy group; and in blood serum samples collected two years after recovering from COVID-19 from patients with (4) T2DM and (5) NfT2DM. It was found that elevated levels of NE and NSE were significantly more common (p &lt; 0.05) in patients with NfT2DM after recovering from COVID-19 compared to the other groups, while elevated levels of S100B were significantly more frequently observed in patients with T2DM after recovering from COVID-19 (p &lt; 0.05). Demonstrating differences in the prevalence of NE, NSE, and S100B in individuals who recovered from COVID-19 with T2DM and NfT2DM makes these proteins important components of the developing predictive model for early detection of PCS. To our knowledge, this is the first study showing the significance of NE, NSE, and S100B in PCS in the context of T2DM and NfT2DM.

The application of interventional methods in control of blood loss during giant upper extremity tumor resection

BackgroundThe purposes of this retrospective study were to determine the efficacy of interventional methods in control of intraoperative blood losses and investigate the perioperative complications.MethodsThe cases of 44 patients in whom a giant upper extremity tumor had been operated between 2008 and 2022 were analyzed retrospectively. Of these, 29 patients were treated with interventional methods (Group A) and 15 were treated without (Group B). Group A was further divided based on the intervention methodss: Group C (combination of balloon occlusion and transarterial embolization [TAE], n = 11) and Group D (single TAE, n = 18). Within Group D, patients were categorized based on the timing of TAE relative to surgery into Group E (TAE on the same day as surgery) and Group F (TAE performed days before surgery). We compared demographic features, blood loss, ICU admission rates, and use of vasopressors during surgery.ResultsWe collected clinical records from 44 patients diagnosed with a giant upper extremity tumor who underwent surgery. Group sizes were as follows: A (29), B (15), C (11), D (18), E (7), and F (11). Tumor volumes in the interventional and non-interventional groups were similar (704.19 ± 812.77 cm³ vs. 1224.53 ± 1414.01 cm³, P = 0.127). Blood plasma transfusion was significantly higher in Group B compared to Group A (425.33 ± 476.20 ml vs. 155.90 ± 269.67 ml, P = 0.021). Although overall blood loss did not significantly differ between Group A and Group B (467.93 ± 302.08 ml vs. 1150 ± 1424.15 ml, P = 0.087), the rate of massive bleeding (defined as blood loss over 1000 ml) was lower in Group A (6.9% vs. 46.47%, P = 0.004). The proportion of minors (patients aged less than 18) in Group C was significantly higher than in Group D (27.7% vs. 0.00%, P = 0.045). The amount of RBC transfusion was also significantly higher in Group C compared to Group D (458.18 ± 292.22 ml vs. 164.44 ± 224.03 ml, P = 0.021). No significant perioperative complications were observed.ConclusionsInterventional techniques have been shown to reduce both blood loss and the necessity for blood transfusions in patients with large upper extremity tumors. Furthermore, no significant perioperative complications have been observed.