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BACKGROUND: The perioperative administration of low-dose ketamine has shown potential in postoperative pain management, opioid sparing, and enhancing pain control. This study aimed to investigate the impact of low-dose ketamine on processed electroencephalography (EEG) signals during anesthesia. METHODS: Forty patients with American Society of Anesthesiologists physical status I-II undergoing elective gynecological surgery were enrolled. EEG monitoring was initiated upon induction of anesthesia. Anesthesia was maintained with desflurane and alfentanil immediately after induction. Fifteen minutes after induction, the ketamine group received a 0.3 mg/kg bolus followed by 0.05 mg/kg/h infusion until completion of surgery. The control group received equivalent saline. Postoperative assessments included pain score (visual analog scale), morphine usage, and quality of recovery. RESULTS: The ketamine group had significantly higher Patient State Index (PSi) values at 10, 20, and 30 minutes after ketamine administration compared to the controls. Ketamine administration led to significant alterations in EEG patterns, including reduced relative power in delta and theta frequency bands, and increased relative power in beta and gamma frequency bands at 10 minutes post-administration. Relative power in the alpha frequency band significantly decreased at 10, 20, and 30 minutes post-administration. However, there were no differences in intraoperative alfentanil consumption, postoperative morphine usage, and pain scores between the two groups. CONCLUSION: Low-dose ketamine administration during desflurane anesthesia led to notable changes in EEG patterns and PSi values. These findings provide valuable insights into the impact of ketamine on brain activity, and offer essential information for clinical anesthesiologists.
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OBJECTIVE: To investigate the risk factors of postoperative delirium in elderly patients undergoing spine surgery. METHODS: The basic case data of 566 patients who underwent spine surgery under general anesthesia from January 2021 to January 2023 were retrospectively analyzed. There were 296 males and 270 females with an average age of (71.58 ± 4.21) years old. There were 195 cases of cervical spine surgery, 26 cases of thoracic spine surgery and 345 cases of lumbar spine surgery.According to the occurrence of postoperative delirium, the patients were divided into postoperative delirium group(41 patients) and non-delirium group (525 patients). Univariate analysis was used to analyze the possible influencing factors such as gender, age, weight, smoking history, drinking history, surgical site, preoperative anxiety, intraoperative hypotension times, blood loss and so on, and binary Logistic regression was used to analyze the univariate factors with P<0.05. RESULTS: A total of 41 patients developed postoperative delirium. Univariate analysis showed that age (P=0.000), duration of surgery (P=0.039), preoperative anxiety (P=0.001), blood loss (P=0.000), history of opioid use (P=0.003), history of stroke (P=0.005), C-reactive protein (P=0.000), sodium ion(P=0.000) were significantly different between delirium group and non-delirium group. These factors were included in the binary Logistic regression analysis, and the results showed that age [OR=0.729, 95%CI(0.569, 0.932), P=0.012], opioid use [OR=21.500, 95%CI(1.334, 346.508), P=0.031], blood loss [OR=0.932, 95%CI(0.875, 0.993), P=0.029], C-reactive protein [OR=0.657, 95%CI(0.485, 0.890), P=0.007], preoperative anxiety [OR=23.143, 95%CI(1.859, 288.090), P=0.015], and sodium [OR=1.228, 95%CI(1.032, 1.461), P=0.020] were independent risk factors for the development of delirium after spinal surgery in elderly patients. CONCLUSION: Age, opioid use, blood loss, preoperative anxiety, elevated c-reactive protein, and hyponatremia are independent risk factors for the development of postoperative delirium in elderly patients undergoing spinal surgery.
Subject(s)
Delirium , Postoperative Complications , Humans , Male , Female , Aged , Risk Factors , Delirium/etiology , Postoperative Complications/etiology , Retrospective Studies , Spine/surgery , Aged, 80 and over , Logistic ModelsABSTRACT
BACKGROUND/AIM: Matrix metalloproteinase-2 (MMP-2) has been implicated in the pathogenesis of breast cancer (BC). However, there is limited research on the role of MMP-2 genotypes in BC risk. This study aimed to investigate the associations between two MMP-2 promoter polymorphisms, rs243865 and rs2285053, and BC risk. MATERIALS AND METHODS: MMP-2 genotypes were analyzed using PCR-based RFLP methodology in a cohort comprising 1,232 BC cases and 1,232 controls. RESULTS: Genotypic frequencies of MMP-2 rs243865 and rs2285053 in controls were consistent with Hardy-Weinberg equilibrium (p=0.3702 and 0.2036, respectively). There were no significant differences in the distribution of rs243865 and rs2285053 genotypes between BC cases and controls (p for trend=0.1602 and 0.2170, respectively). Variant genotypes at rs243865 and rs2285053 appeared to confer a protective effect, although not statistically significant (all p>0.05). Similarly, the variant T allele at rs243865 and rs2285053 showed a non-significant trend towards decreased BC risk (OR=0.84 and 0.89, 95%CI=0.69-1.02 and 0.78-1.02, p=0.0811 and 0.1043, respectively). There was no interaction observed between MMP-2 rs243865 or rs2285053 genotypes and age. Stratified analysis did not reveal significant associations between MMP-2 rs243865 or rs2285053 genotypes and triple-negative breast cancer (TNBC) (p=0.6458 and 0.8745, respectively). Among both TNBC and non-TNBC cases, none of the variant genotypes at rs243865 or rs2285053 showed significant associations with TNBC (all p>0.05). CONCLUSION: MMP-2 rs243865 and rs2285053 genotypes appear to have a minimal impact on individual susceptibility to BC or TNBC.
Subject(s)
Breast Neoplasms , Genetic Predisposition to Disease , Genotype , Matrix Metalloproteinase 2 , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Humans , Matrix Metalloproteinase 2/genetics , Female , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Middle Aged , Adult , Case-Control Studies , Risk FactorsABSTRACT
To reduce the use of antibiotics and chemicals in aquaculture, an edible herb, Bidens pilosa, has been selected as a multifunctional feed additive. Although there has been considerable research into the effects of B. pilosa on poultry, the wider effects of B. pilosa, particularly on the growth and gut microbiota of fish, remain largely unexplored. We aimed to investigate the interactive effects between the host on growth and the gut microbiota using transcriptomics and the gut microbiota in B. pilosa-fed tilapia. In this study, we added 0.5% and 1% B. pilosa to the diet and observed that the growth performance of tilapia significantly increased over 8 weeks of feeding. Comparative transcriptome analysis was performed on RNA sequence profiles obtained from liver and muscle tissues. Functional enrichment analysis revealed that B. pilosa regulates several pathways and genes involved in amino acid metabolism, lipid metabolism, carbohydrate metabolism, endocrine system, signal transduction, and metabolism of other amino acids. The expression of the selected growth-associated genes was validated by qRT-PCR. The qRT-PCR results indicated that B. pilosa may enhance growth performance by activating the expression of the liver igf1 and muscle igf1rb genes and inhibiting the expression of the muscle negative regulator mstnb. Both the enhancement of liver endocrine IGF1/IGF1Rb signaling and the suppression of muscle autocrine/paracrine MSTN signaling induced the expression of myogenic regulatory factors (MRFs), myod1, myog and mrf4 in muscle to promote muscle growth in tilapia. The predicted function of the gut microbiota showed several significantly different pathways that overlapped with the KEGG enrichment results of differentially expressed genes in the liver transcriptomes. This finding suggested that the gut microbiota may influence liver metabolism through the gut-liver axis in B. pilosa-fed tilapia. In conclusion, dietary B. pilosa can regulate endocrine IGF1 signaling and autocrine/paracrine MSTN signaling to activate the expression of MRFs to promote muscle growth and alter the composition of gut bacteria, which can then affect liver amino acid metabolism, carbohydrate metabolism, endocrine system, lipid metabolism, metabolism of other amino acids, and signal transduction in the host, ultimately enhancing growth performance. Our results suggest that B. pilosa has the potential to be a functional additive that can be used as an alternative to reduce antibiotic use as a growth promoter in aquaculture.
Subject(s)
Animal Feed , Bidens , Gastrointestinal Microbiome , Tilapia , Animals , Gastrointestinal Microbiome/drug effects , Tilapia/growth & development , Tilapia/microbiology , Tilapia/genetics , Tilapia/metabolism , Bidens/metabolism , Bidens/growth & development , Gene Expression Profiling , Transcriptome , Liver/metabolismABSTRACT
BACKGROUND/AIM: In current literature, there is a notable lack of studies investigating the role of radiation-sensitive protein 51 (RAD-51) in pterygium diagnosis. Nevertheless, reports indicate elevated expression levels of RAD-51 among recurrent pterygium cases compared to those with primary pterygium. However, the genomic involvement of RAD-51 has yet to be explored in any population. This study aimed to assess the contribution of RAD-51 genotypes to pterygium risk in a representative Taiwanese population. MATERIALS AND METHODS: RAD-51 rs1801320 genotyping was successfully conducted in a Taiwanese cohort comprising 140 pterygium cases and 280 non-pterygium controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technology. RESULTS: The distribution of RAD-51 rs1801320 genotypes (GG, CG, and CC) in the pterygium group (70.0%, 25.7%, and 4.3%, respectively) did not significantly differ from that in the non-pterygium group (73.6%, 23.6%, and 2.8% for GG, CG, and CC genotypes, respectively; p for trend=0.6337). Carriers of the variant CG and CC RAD-51 rs1801320 genotypes exhibited 1.15- and 1.58-fold increased pterygium risk, respectively (95%CI=0.72-1.84 and 0.53-4.67, p=0.6552 and p=0.5914, respectively). In the dominant model, there appeared to be a slight association between variant genotypes CG and CC and pterygium risk (OR=1.19, 95%CI=0.76-1.87, p=0.0223). Allelic analysis revealed that the RAD-51 rs1801320 variant C allele was not significantly linked to pterygium risk (17.1% versus 14.6%, OR=1.20, 95%CI=0.82-1.78, p=0.3991). CONCLUSION: Variant genotypes at RAD-51 rs1801320 were firstly identified to associate with susceptibility to pterygium among Taiwanese individuals. Nonetheless, these findings warrant validation in larger and more diverse populations.
Subject(s)
Genetic Predisposition to Disease , Genotype , Polymorphism, Single Nucleotide , Pterygium , Humans , Pterygium/genetics , Pterygium/etiology , Male , Female , Taiwan/epidemiology , Middle Aged , Aged , Rad51 Recombinase/genetics , Alleles , Risk Factors , Case-Control Studies , Gene Frequency , AdultABSTRACT
BACKGROUND/AIM: The overexpression of matrix metalloproteinase-9 (MMP9) has been observed in asthmatic patients, yet the role of MMP9 genotype in determining asthma susceptibility remains unresolved. This study aimed to elucidate the contribution of MMP9 promoter rs3918242 genotype to asthma risk in Taiwan. MATERIALS AND METHODS: A cohort comprising 453 non-asthmatic healthy controls and 198 asthmatic cases was assembled, and the MMP9 rs3918242 genotypes were determined using polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: Our findings indicated that people carrying the variant CT or TT genotype of MMP9 rs3918242 did not demonstrate an elevated risk of asthma compared to wild-type CC carriers (odds ratio=1.28 and 1.72, 95% confidence interval=0.87-1.87 and 0.72-4.13; p=0.2417 and 0.3201, respectively). Furthermore, individuals carrying the T allele at MMP9 rs3918242 did not exhibit a higher risk of asthma than those carrying the C allele (odds ratio=1.31, 95% confidence interval=0.96-1.79, p=0.0869). Interestingly, a positive association was observed between MMP9 rs3918242 CT or TT genotypes and the severity of asthma symptoms among asthmatic patients (p=0.0035). CONCLUSION: Although the T allele at MMP9 rs3918242 was not associated with asthma risk, it may serve as a predictor for asthma symptom severity. These findings warrant validation in larger and more diverse populations to further elucidate the significance of MMP9 in asthma etiology.
Subject(s)
Alleles , Asthma , Genetic Predisposition to Disease , Genotype , Matrix Metalloproteinase 9 , Polymorphism, Single Nucleotide , Promoter Regions, Genetic , Humans , Asthma/genetics , Matrix Metalloproteinase 9/genetics , Male , Female , Middle Aged , Adult , Case-Control Studies , Taiwan/epidemiology , Risk Factors , Gene Frequency , Odds Ratio , Genetic Association StudiesABSTRACT
[This corrects the article DOI: 10.3389/fimmu.2022.967040.].
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BACKGROUND: Purpose: High-flow nasal cannula (HFNC) has many benefits in various clinical conditions. The original hypothesis suggests that the high and constant fraction of inspired oxygen (FiO2) is one of the main physiological effects. However, increasing evidence shows that there is a gap between the actual FiO2 and administered FiO2. We aimed to determine the actual FiO2 under different respiratory conditions and develop a regression model using a spontaneous breathing lung model. METHODS: A spontaneous breathing simulation model was built using an airway manikin and a model lung. The FiO2 was measured under different respiratory conditions with varying tidal volumes and respiratory and HFNC flow rates. The relationships between the respiratory parameters and actual FiO2 were determined and used to build the predictive model. RESULTS: The actual FiO2 was negatively correlated with respiratory rate and tidal volume and positively correlated with HFNC flow. The regression model could not be developed using simple respiratory parameters. Therefore, we introduced a new variable, defined as flow ratio, which equaled the HFNC flow divided by inspiratory flow. Our equation demonstrated that the actual FiO2 was mainly determined by the flow ratio in a non-linear relationship. Accordingly, a flow ratio greater than 1 did not ensure a constant high FiO2, whereas a flow ratio >1.435 could produce FiO2 >0.9. CONCLUSION: The FiO2 during HFNC was not constant even at sufficiently high oxygen flow compared with inspiratory flow. The predictive model showed that the actual FiO2 was mainly determined by the flow ratio.
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Air insoles have provided insights for reducing the risk of diabetic foot ulcers (DFU). The pressure time integral (PTI) is an effective assessment that considers the time effect in various physical activities. We investigated the interactions between three different insole inner pressures (80, 160, and 240 mmHg) and two walking durations (10 and 20 min). The big toe (T1), first metatarsal head (M1), and second metatarsal head (M2) were investigated in 13 healthy participants. One-way analysis of variance (ANOVA) showed that the effects of each insole inner pressure significantly differed (P < 0.05) with a 10 min walking duration. The PTI values resulting from 80 mmHg in M2 (38.4 ± 3.8, P = 0.002) and 160 mmHg in M1 (44.3 ± 4.3, P = 0.027) were lower than those from 240 mmHg. Additionally, the paired t test showed that the effects of each walking duration were also considerably different at 160 mmHg. The PTI at 10 min was lower than that at 20 min in M1 (44.31 ± 4.31, P = 0.015) and M2 (47.14 ± 5.27, P = 0.047). Thus, we suggest that walking with a pressure of 160 mmHg for 10 min has a lower risk of DFU.
Subject(s)
Foot , Pressure , Walking , Humans , Walking/physiology , Male , Female , Adult , Foot/physiology , Foot Orthoses , Diabetic Foot/prevention & control , Diabetic Foot/therapy , Shoes , Young Adult , Time FactorsABSTRACT
OBJECTIVES: To investigate whether chronotype is a moderator variable that also interacts with shift type and whether they jointly influence the attention performance of nurses working in acute and critical care units. METHODS: We adopted a longitudinal research design focusing on nurses working rotating shifts in the emergency room and intensive care units at a medical center. A total of 40 complete samples were obtained. Data analysis was conducted using the generalized estimating equations in SAS 9.4. RESULTS: The mean (SD) age of the participants was 26.35 (2.12) years. After controlling for age, gender, and sleep duration, an interaction effect was discovered between a specific chronotype and shift type; that is, the interaction effect between chronotype and shift type was only significant when comparing late-types working the night shift with early- and intermediate-types working the night shift (B = -18.81, P = .011). The least squares means of the mean reaction time of the interaction effects between the 2 chronotype groups and the 3 shift types found that the mean reaction time of late-types working the night shift was 11.31 ms (P = .044) slower compared with working the day shift. CONCLUSIONS: The chronotype is a moderator variable between shift type and mean reaction time, such that matching the chronotype of nurses in acute and critical care units with the appropriate shift type improved their mean reaction time. It is hoped that the results of this study could serve as a reference for acute and critical care nurses when scheduling their shifts.
Subject(s)
Attention , Nursing Staff, Hospital , Shift Work Schedule , Work Schedule Tolerance , Humans , Adult , Female , Male , Longitudinal Studies , Nursing Staff, Hospital/psychology , Work Schedule Tolerance/physiology , Circadian Rhythm , Intensive Care Units , Reaction Time , Sleep , Critical Care Nursing , Young Adult , Emergency Service, Hospital , ChronotypeABSTRACT
Physical exercise requires integrated autonomic and cardiovascular adjustments to maintain homeostasis. We aimed to observe acute posture-related changes in blood pressure, and apply a portable noninvasive monitor to measure the heart index for detecting arrhythmia among elite participants of a 246-km mountain ultra-marathon. Nine experienced ultra-marathoners (8 males and 1 female) participating in the Run Across Taiwan Ultra-marathon in 2018 were enrolled. The runners' Heart Spectrum Blood Pressure Monitor measurements were obtained in the standing and supine positions before and immediately after the race. Their high-sensitivity troponin T and N-terminal proB-type natriuretic peptide levels were analyzed 1 week before and immediately after the event. Heart rate was differed significantly in the immediate postrace assessment compared to the prerace assessment, in both the standing (Pâ =â .011; dâ =â 1.19) and supine positions (Pâ =â .008; dâ =â 1.35). Postural hypotension occurred in 4 (44.4%) individuals immediately postrace. In 3 out of 9 (33.3%) recruited finishers, the occurrence of premature ventricular complex signals in the standing position was detected; premature ventricular complex signal effect was observed in the supine position postrace in only 1 participant (11.1%). Premature ventricular complex signal was positively correlated with running speed (Pâ =â .037). Of the 6 individuals who completed the biochemical tests postrace, 2 (33.3%) had high-sensitivity troponin T and 6 (100%) had N-terminal proB-type natriuretic peptide values above the reference interval. A statistically significant increase was observed in both the high-sensitivity troponin T (Pâ =â .028; dâ =â 1.97), and N-terminal proB-type natriuretic peptide (Pâ =â .028; dâ =â 2.91) levels postrace compared to prerace. In conclusion, significant alterations in blood pressure and heart rate were observed in the standing position, and postexercise (postural) hypotension occurred among ultra-marathoners. The incidence of premature ventricular complexes was higher after the race than before.
Subject(s)
Autonomic Nervous System , Blood Pressure , Heart Rate , Marathon Running , Natriuretic Peptide, Brain , Troponin T , Humans , Female , Male , Autonomic Nervous System/physiology , Heart Rate/physiology , Marathon Running/physiology , Adult , Troponin T/blood , Middle Aged , Blood Pressure/physiology , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Taiwan , Ventricular Premature Complexes/physiopathology , Ventricular Premature Complexes/diagnosis , Hypotension, Orthostatic/physiopathology , Posture/physiologyABSTRACT
BACKGROUND: Rotating-shift nurses are susceptible to sleep disorders due to numerous factors, such as their biological clock, emotions, and age. At present, a lack of research exists on whether chronotype and shift type jointly influence the sleep quality of nurses. AIM: To verify whether chronotype is a moderator variable of the relationship between shift type and sleep quality in nurses in order to provide empirical evidence for future mental and physical health improvement. METHOD: Clinical rotating-shift nurses at a medical center in northern Taiwan were recruited as participants between November 1, 2023, and December 13, 2023. All of the nurses were working a monthly rotating shift schedule. Hierarchical multiple regression analysis was employed to investigate whether the influence of shift type on sleep quality in nurses varied with chronotype. The STROBE checklist was used for reporting this study. RESULTS: The participants were 255 rotating-shift nurses in this study. Hierarchical multiple regression results revealed that rotating-shift nurses who were older (B = 0.19, p = 0.029), had greater physical fatigue (B = 0.27, p = 0.016), and had more negative emotions (B = 0.17, p = 0.011) suffered from poorer sleep quality. After controlling the above factors, we further found that chronotype indeed had moderating effects on the influence of shift type on sleep quality (B = -1.83, p = 0.049). CONCLUSIONS: This study demonstrates that early- and intermediate-type nurses are more suitable for working the day and evening shifts, whereas late-type nurses are more suitable for working the night shift. IMPLICATION FOR NURSING AND HEALTH POLICY: Coordinating chronotype with shift type will ensure that shift schedules better match the biological clocks of nurses; such individual considerations could help to improve their sleep quality.
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Background: Previous research has hinted at a crucial link between gut microbiota and arterial embolism and thrombosis, yet the causal relationship remains enigmatic. To gain a deeper understanding, we aimed to comprehensively explore the causal relationship and elucidate the impact of the gut microbiota on the risk through a two-sample Mendelian randomization (MR) study. Methods: Genetic instrumental variables for gut microbiota were identified from a genome-wide association study (GWAS) of 18,340 participants. Summary statistics for IBS were drawn from a GWAS including 1,076 cases and 381,997 controls. We used the inverse-variance weighted (IVW) method as the primary analysis. To test the robustness of our results, we further performed the weighted median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test. Results: We identified three bacterial traits that were associated with the risk of arterial embolism and thrombosis: odds ratio (OR): 1.58, 95% confidence interval (CI): 1.08-2.31, p = 0.017 for genus Catenibacterium; OR: 0.64, 95% CI: 0.42-0.96, p = 0.031 for genus Dialister; and OR: 2.08, 95% CI: 1.25-3.47, p = 0.005 for genus Odoribacter. The results of sensitivity analyses for these bacterial traits were consistent (P<0.05). Conclusion: Our systematic analyses provided evidence to support a potential causal relationship between several gut microbiota taxa and the risk of arterial embolism and thrombosis. More studies are required to show how the gut microbiota affects the development of arterial embolism and thrombosis.
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OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.
Subject(s)
Spermatogenesis , Testis , Animals , Male , Spermatogenesis/genetics , Mice , Testis/metabolism , Spermatogonia/metabolism , Spermatogonia/cytology , Phylogeny , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Gene Expression ProfilingABSTRACT
Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells.
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BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. CONCLUSIONS: Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.
Subject(s)
DNA Methylation , Epigenesis, Genetic , Cattle , Animals , Humans , CpG Islands , Genetic VariationABSTRACT
Matrix metalloproteinase (MMP)-2 and -9, which degrade type IV collagen, are linked to cancer invasion and metastasis. Gene polymorphisms in MMP-2 and MMP-9 can influence their function, impacting cancer development and progression. This study analyzed the association between polymorphisms MMP-2 rs243865 (C-1306T), rs2285053 (C-735T), and MMP-9 rs3918242 (C-1562T) with serum concentrations of these enzymes in upper tract urothelial cancer (UTUC) patients. We conducted a case-control study with 218 UTUC patients and 580 healthy individuals in Taiwan. Genotyping was performed using PCR/RFLP on DNA from blood samples, and MMP-2 and MMP-9 serum levels and mRNA expressions in 30 UTUC patients were measured using ELISA and real-time PCR. Statistical analysis showed that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes were differently distributed between UTUC patients and controls (p = 0.0199 and 0.0020). The MMP-2 rs2285053 TT genotype was associated with higher UTUC risk compared to the CC genotype (OR = 2.20, p = 0.0190). Similarly, MMP-9 rs3918242 CT and TT genotypes were linked to increased UTUC risk (OR = 1.51 and 2.92, p = 0.0272 and 0.0054). In UTUC patients, TT carriers of MMP-2 rs2285053 and MMP-9 rs3918242 showed higher mRNA and protein levels (p < 0.01). These findings suggest that MMP-2 rs2285053 and MMP-9 rs3918242 genotypes are significant markers for UTUC risk and metastasis in Taiwan.
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Early rehabilitation has beneficial impacts on functional outcomes for patients with acute stroke. However, whether the addition of virtual reality (VR) training could further improve these patients' muscle strength, functional recovery, and psychological health is unknown. A randomized controlled trial was conducted on 33 patients with first-time acute ischemic stroke. The patients were randomly assigned using a 1:1 randomization ratio to either the experimental group (EG) or the comparison group (CG). Both groups received early rehabilitation, and the EG received extra VR training during their stay in the hospital. Muscle strength, functional status, and psychological health were assessed before the intervention and at discharge. Generalized estimating equations were used to examine the intervention effects via the interaction of time and group. After adjusting for potential covariates, the EG showed a more significant decrease in depression at discharge than the CG (ß = 3.77, p = 0.011). There were no differences in muscle strength and functional recovery between groups after intervention. Adding VR training into early rehabilitation facilitates substantial positive effects on psychological health, specifically depression, but not muscle strength and functional recovery, compared to receiving early rehabilitation alone in patients with first-time acute stroke during their hospitalized period.