ABSTRACT
OBJECTIVE: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles. METHODS: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group (n = 230):18.5 kg/m2≤BMI < 24 kg/m2; overweight group (n = 122): 24 kg/m2≤BMI < 28 kg/m2; Obesity group (n = 60): BMI ≥ 28 kg/m2. Variables with p < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol. RESULTS: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p < .05). CONCLUSION: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.
Subject(s)
Body Mass Index , Gonadotropin-Releasing Hormone , Ovulation Induction , Progesterone , Humans , Female , Gonadotropin-Releasing Hormone/antagonists & inhibitors , Progesterone/blood , Adult , Retrospective Studies , Ovulation Induction/methods , Hormone Antagonists/administration & dosage , Hormone Antagonists/therapeutic use , Fertilization in Vitro/methods , Obesity/blood , Overweight/blood , Sperm Injections, Intracytoplasmic , PregnancyABSTRACT
Bladder cancer is characterized by aberrant activation of the phosphatidylinositol-3-OH kinase (PI3K) signaling, underscoring the significance of directing therapeutic efforts toward the PI3K pathway as a promising strategy. In this study, we discovered that PI3K serves as a potent therapeutic target for bladder cancer through a high-throughput screening of inhibitory molecules. The PI3K inhibitor demonstrated a robust anti-tumor efficacy, validated both in vitro and in vivo settings. Nevertheless, the feedback activation of JAK1-STAT3 signaling reinstated cell and organoid survival, leading to resistance against the PI3K inhibitor. Mechanistically, the PI3K inhibitor suppresses PTPN11 expression, a negative regulator of the JAK-STAT pathway, thereby activating STAT3. Conversely, restoration of PTPN11 enhances the sensitivity of cancer cells to the PI3K inhibitor. Simultaneous inhibition of both PI3K and STAT3 with small-molecule inhibitors resulted in sustained tumor regression in patient-derived bladder cancer xenografts. These findings advocate for a combinational therapeutic approach targeting both PI3K and STAT3 pathways to achieve enduring cancer eradication in vitro and in vivo, underscoring their promising therapeutic efficacy for treating bladder cancer.
ABSTRACT
We conducted a study on the trajectory-dependent threshold effects of proton stopping power in LiF nanosheets using time-dependent density functional theory non-adiabatically coupled to the molecular dynamics. This study covered protons with initial velocities in the range of 0.1-1.0 a.u., offering a vast amount of detailed information on the electronic structure during the stopping process with superior spatial and temporal resolution. Our results show that the impact parameters of incident protons play a crucial role in determining the threshold behavior of proton stopping power in LiF nanosheets. Most importantly, we found that close collisions do not exhibit a discernible threshold. In addition, the research results also revealed the time dependence of the number of electrons occupying the atomic orbitals of F and Li as protons pass through the nanosheets.
ABSTRACT
BACKGROUND: Inflammatory bowel disease is a common digestive disorder and diabetes can lead to intestinal dysfunction. Patients with inflammatory bowel disease in combination with diabetes present a higher rate of hospitalization and consumption of medical resources, yet the association between type 2 diabetes and Inflammatory bowel disease remains unknown. METHODS: We studied 313,008 participants from the UK Biobank, including 5891 patients with type 2 diabetes at baseline. Multivariate Cox proportional risk models were constructed to examine the risks associated with type 2 diabetes and inflammatory bowel disease and its subtypes (Crohn's disease, ulcerative colitis). Potential confounders including sociodemographic, lifestyle, physical body indicators, psychological state, hypertension, and thyroid-related disorders were adjusted. Propensity score matching was also performed to analyze their sensitivity. RESULTS: Of a total of 313,008 participants included in the study, 5891 (1.88 %) were diagnosed with type 2 diabetes mellitus at baseline and 1829 (0.58 %) of the entire cohort developed inflammatory bowel disease during follow-up, with a median follow-up time of 13.72 years. Patients with type 2 diabetes had a higher cumulative risk of inflammatory bowel disease compared to the non-type 2 diabetes population (inflammatory bowel disease: 1.24% vs. 0.57%, p < 0.001; Crohn's disease: 0.46% vs. 0.15%, p < 0.001; ulcerative colitis: 0.73% vs. 0.35%, p < 0.001). Multivariate Cox regression analysis showed that type 2 diabetes was independently associated with inflammatory bowel disease (Hazard Ratio: 1.61 [95% Confidence Interval: 1.26-2.06], p < 0.001), Crohn's disease (Hazard Ratio: 2.10 [95% Confidence Interval: 1.39-3.17], p < 0.001) and ulcerative colitis (Hazard Ratio: 1.58 [95% Confidence Interval: 1.15-2.18], p = 0.005). In a propensity-matched analysis, type 2 diabetes still showed its ability to predict the risk of inflammatory bowel disease (Hazard Ratio: 2.09 [95% Confidence Interval: 1.55-2.83], p < 0.001), Crohn's disease (Hazard Ratio: 3.49 [95% Confidence Interval: 2.00 to 6.09], p < 0.001), and ulcerative colitis (Hazard Ratio: 1.76 [95% Confidence Interval: 1.20 to 2.56], p = 0.003) of robustness. CONCLUSION: In patients with type 2 diabetes mellitus, the risk of inflammatory bowel disease is higher, and the presence of gastrointestinal symptoms in patients with type 2 diabetes requires vigilance for the possibility of inflammatory bowel disease in clinical practice.
Subject(s)
Diabetes Mellitus, Type 2 , Inflammatory Bowel Diseases , Humans , Male , Female , Prospective Studies , Middle Aged , Risk Factors , Inflammatory Bowel Diseases/complications , Adult , United Kingdom/epidemiology , Aged , Proportional Hazards Models , Crohn Disease/complicationsABSTRACT
Previous studies have suggested that exposure to air pollutants may be associated with specific blood indicators or anemia in certain populations. However, there is insufficient epidemiological data and prospective evidence to evaluate the relationship between environmental air pollution and specific types of anemia. We conducted a large-scale prospective cohort study based on the UK Biobank. Annual average concentrations of NO2, PM2.5, PM2.5-10, and PM10 were obtained from the ESCAPE study using the Land Use Regression (LUR) model. The association between atmospheric pollutants and different types of anemia was investigated using the Cox proportional hazards model. Furthermore, restricted cubic splines were used to explore exposure-response relationships for positive associations, followed by stratification and effect modification analyses by gender and age. After adjusting for demographic characteristics, 3-4 of the four types of air pollution were significantly associated with an increased risk of iron deficiency, vitamin B12 deficiency and folate deficiency anemia, while there was no significant association with other defined types of anemia. After full adjustment, we estimated that the hazard ratios (HRs) of iron deficiency anemia associated with each 10 µg/m3 increase in NO2, PM2.5, and PM10 were 1.04 (95%CI: 1.02, 1.07), 2.00 (95%CI: 1.71, 2.33), and 1.10 (95%CI: 1.02, 1.20) respectively. The HRs of folate deficiency anemia with each 10 µg/m3 increase in NO2, PM2.5, PM2.5-10, and PM10 were 1.25 (95%CI: 1.12, 1.40), 4.61 (95%CI: 2.03, 10.47), 2.81 (95%CI: 1.11, 7.08), and 1.99 (95%CI: 1.25, 3.15) respectively. For vitamin B12 deficiency anemia, no significant association with atmospheric pollution was found. Additionally, we estimated almost linear exposure-response curves between air pollution and anemia, and interaction analyses suggested that gender and age did not modify the association between air pollution and anemia. Our research provided reliable evidence for the association between long-term exposure to PM10, PM2.5, PM2.5-10, NO2, and several types of anemia. NO2, PM2.5, and PM10 significantly increased the risk of iron deficiency anemia and folate deficiency anemia. Additionally, we found that the smaller the PM diameter, the higher the risk, and folate deficiency anemia was more susceptible to air pollution than iron deficiency anemia. No association was observed between the four types of air pollution and hemolytic anemia, aplastic anemia, and other types of anemia. Although the mechanisms are not well understood, we emphasize the need to limit the levels of PM and NO2 in the environment to reduce the potential impact of air pollution on folate and iron deficiency anemia.
Subject(s)
Air Pollutants , Anemia , Particulate Matter , Humans , Male , Female , Air Pollutants/analysis , Air Pollutants/adverse effects , Middle Aged , United Kingdom/epidemiology , Particulate Matter/analysis , Particulate Matter/adverse effects , Anemia/epidemiology , Anemia/blood , Prospective Studies , Aged , Adult , Nitrogen Dioxide/analysis , Nitrogen Dioxide/adverse effects , Proportional Hazards Models , Biological Specimen Banks , Risk Assessment , Air Pollution/adverse effects , Air Pollution/analysis , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Folic Acid Deficiency/epidemiology , Folic Acid Deficiency/blood , UK BiobankABSTRACT
BACKGROUND: There is a close association between diet and abdominal pain; however, relationship between inflammatory diet and characteristics of abdominal pain has not been characterized yet. METHODS: This study analyzed baseline data from the UK Biobank, 3-item DHQ-Abdominal Pain Questionnaire (DHQ-3Q), which including abdominal pain in the past 3 months, severity of abdominal pain, and frequency of abdominal pain, and data from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Energy-adjusted Dietary Inflammatory Index (E-DII), constructed based on 26 or 27 nutrients, was analyzed using continuous or categorical methods. Logistic regression and restricted cubic spline analyses examined the association between E-DII and abdominal pain. RESULTS: In UK Biobank, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.12 (95% CI 1.02-1.24; P = .022), 1.05 (95% CI 1.00-1.09; P = .030), 1.26 (95% CI 1.17-1.36; P < .001), and 1.10 (95% CI 1.00-1.20; P = .044) for chronic abdominal pain, abdominal pain in the past three months, severity of abdominal pain, and frequency of abdominal pain, respectively. In NHANES, compared to participants in the lowest quintile of E-DII, the adjusted ORs for the highest quintile were 1.46 (95% CI 1.20-1.77;P < .001), 1.75 (95% CI 1.20-2.60; P = .005), 1.45 (95% CI 1.14-1.87; P = .003), and 1.18 (95% CI 0.82-1.72; P = .380) for abdominal pain in the past year, upper left abdominal pain, upper middle abdominal pain, and upper right abdominal pain. Additionally, there was a nonlinear correlation between E-DII score and DHQ-3Q (P nonlinear <.001). CONCLUSION: Following a pro-inflammatory diet is linked to a higher likelihood of experiencing abdominal pain, as well as increased severity and frequency of such pain. Therefore, further longitudinal studies are necessary to investigate this relationship.
Subject(s)
Abdominal Pain , Diet , Nutrition Surveys , Humans , Abdominal Pain/epidemiology , Female , Male , Middle Aged , United Kingdom/epidemiology , Cross-Sectional Studies , Case-Control Studies , Aged , Adult , Inflammation , Biological Specimen Banks , UK BiobankABSTRACT
Breastfeeding is widely recognized as the gold standard for infant nutrition, benefitting infants' gastrointestinal tracts. Stool analysis helps in understanding pediatric gastrointestinal health, but the effectiveness of automated fecal consistency evaluation by parents of breastfeeding infants has not been investigated. Photographs of one-month-old infants' feces on diapers were taken via a smartphone app and independently categorized by Artificial Intelligence (AI), parents, and researchers. The accuracy of the evaluations of the AI and the parents was assessed and compared. The factors contributing to assessment bias and app user characteristics were also explored. A total of 98 mother-infant pairs contributed 905 fecal images, 94.0% of which were identified as loose feces. AI and standard scores agreed in 95.8% of cases, demonstrating good agreement (intraclass correlation coefficient (ICC) = 0.782, Kendall's coefficient of concordance W (Kendall's W) = 0.840, Kendall's tau = 0.690), whereas only 66.9% of parental scores agreed with standard scores, demonstrating low agreement (ICC = 0.070, Kendall's W = 0.523, Kendall's tau = 0.058). The more often a mother had one or more of the following characteristics, unemployment, education level of junior college or below, cesarean section, and risk for postpartum depression (PPD), the more her appraisal tended to be inaccurate (p < 0.05). Each point increase in the Edinburgh Postnatal Depression Scale (EPDS) score increased the deviation by 0.023 points (p < 0.05), which was significant only in employed or cesarean section mothers (p < 0.05). An AI-based stool evaluation service has the potential to assist mothers in assessing infant stool consistency by providing an accurate, automated, and objective assessment, thereby helping to monitor and ensure the well-being of infants.
Subject(s)
Breast Feeding , Mothers , Humans , Infant , Child , Female , Pregnancy , Cohort Studies , Artificial Intelligence , Cesarean Section , ChinaABSTRACT
The telomerase reverse transcriptase promoter (TERTp) is frequently mutated in gliomas. This study sought to identify immune biomarkers of gliomas with TERTp mutations. Data from TCGA were used to identify and validate survival-associated gene signatures, and immune and stromal scores were calculated using the ESTIMATE algorithm. High stromal or immune scores in patients with TERTp-mutant gliomas correlated with shorter overall survival compared to cases with low stromal or immune scores. Among TERTp-mutant gliomas with both high immune and high stromal scores, 213 commonly shared DEGs were identified. Among 71 interacting DEGs representing candidate hub genes in a PPI network, HOXC6, WT1, CD70, and OTP showed significant ability in establishing subgroups of high- and low-risk patients. A risk model based on these 4 genes showed strong prognostic potential for gliomas with mutated TERTp, but was inapplicable for TERTp-wild-type gliomas. TERTp-mutant gliomas with high-risk scores displayed a greater percentage of naïve B cells, plasma cells, naïve CD4 T cells, and activated mast cells than low-risk score gliomas. TIDE analysis indicated that immune checkpoint blockade (ICB) therapy may benefit glioma patients with TERTp mutations. The present risk model can help predict prognosis of glioma patients with TERTp mutations and aid ICB treatment options.
Subject(s)
Brain Neoplasms , Glioma , Telomerase , Humans , Immune Checkpoint Inhibitors/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Mutation , Glioma/drug therapy , Glioma/genetics , Prognosis , Telomerase/geneticsABSTRACT
The objective of this study was to examine the sensory interactions between lactones and ketones in a Cheddar simulation matrix through perceptual interaction analysis. The olfactory thresholds of 6 key lactones had values ranging from 8.32 to 58.88 µg/kg, whereas those of the 4 key ketones ranged from 6.61 to 660.69 µg/kg. Both Feller's additive model and σ-τ plots demonstrated complex interactions in 24 binary mixtures composed of the 6 lactones and 4 ketones, including synergy, addition, and masking effects. Specifically, we found that 6 binary mixtures exhibited aroma synergistic effects using both methods. Moreover, the σ-τ plot showed a synergistic effect of aroma in 3 ternary mixtures. The U-model further confirmed the synergistic effects of the 6 groups of binary systems and 3 groups of ternary systems on aroma at actual cheese concentrations. In an aroma addition experiment, the combination of δ-octalactone and diacetyl in binary mixtures had the most pronounced effect on enhancing milk flavor. In ternary mixtures, 2 combinations, namely δ-octalactone/δ-dodecalactone/diacetyl and γ-dodecalactone/δ-dodecalactone/acetoin, significantly enhanced the milky and sweet aroma properties of cheese, while also enhancing the overall acceptability of the cheese aroma.
Subject(s)
Cheese , Ketones , Lactones , Odorants , Cheese/analysis , Ketones/analysis , Animals , Taste , Milk/chemistryABSTRACT
BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.
Subject(s)
Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Cell Line, Tumor , Lymphatic Metastasis , Carcinoma, Ovarian Epithelial , Cell Proliferation , Transcription Factors/genetics , Homeodomain ProteinsABSTRACT
During meiosis, cohesin and meiosis-specific proteins organize chromatin into an axis-loop architecture, coordinating homologous synapsis, recombination, and ordered chromosome segregation. However, how the meiotic chromosome axis is assembled and differentiated with meiotic progression remains elusive. Here, we explore the dynamic recruitment of two long arms of the bivalent proteins, LAB-1 and LAB-2, in Caenorhabditis elegans. LAB proteins directly interact with the axis core HORMA complexes and weak interactions contribute to their recruitment. LAB proteins phase separate in vitro, and this capacity is promoted by HORMA complexes. During early prophase, synapsis oppositely regulates the axis enrichment of LAB proteins. After the pachytene exit, LAB proteins switch from a reciprocal localization pattern to a colocalization pattern, and the normal dynamic pattern of LAB proteins is altered in meiotic mutants. We propose that LAB recruitment senses axis differentiation, and phase separation of meiotic structures helps subdomain establishment and accurate segregation of the chromosomes.
Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Chromosomal Proteins, Non-Histone , Meiosis , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Chromosome Pairing/genetics , Chromosome Segregation , Chromosomes/genetics , Chromosomes/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolismABSTRACT
Over the course of long-term evolution, cells have developed intricate defense mechanisms in response to DNA damage; these mechanisms play a pivotal role in maintaining genomic stability. Defects in the DNA damage response pathways can give rise to various diseases, including cancer. The DNA damage response (DDR) system is instrumental in safeguarding genomic stability. The accumulation of DNA damage and the weakening of DDR function both promote the initiation and progression of tumors. Simultaneously, they offer opportunities and targets for cancer therapeutics. This article primarily elucidates the DNA damage repair pathways and the progress made in targeting key proteins within these pathways for cancer treatment. Among them, poly (ADP-ribose) polymerase 1 (PARP1) plays a crucial role in DDR, and inhibitors targeting PARP1 have garnered extensive attention in anticancer research. By delving into the realms of DNA damage and repair, we aspire to explore more precise and effective strategies for cancer therapy and to seek novel avenues for intervention.
Subject(s)
DNA Repair , Neoplasms , Humans , Poly(ADP-ribose) Polymerase Inhibitors/pharmacology , Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use , DNA Damage , Poly (ADP-Ribose) Polymerase-1/genetics , Poly (ADP-Ribose) Polymerase-1/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Genomic InstabilityABSTRACT
BACKGROUND: Microbiota alterations are linked with gastric cancer (GC). However, the relationship between the oral microbiota (especially oral fungi) and GC is not known. In this study, we aimed to apply 2b-RAD sequencing for Microbiome (2b-RAD-M) to characterize the oral microbiota in patients with GC. METHODS: We performed 2b-RAD-M analysis on the saliva and tongue coating of GC patients and healthy controls. We carried out diversity, relative abundance, and composition analyses of saliva and tongue coating bacteria and fungi in the two groups. In addition, indicator analysis, the Gini index, and the mean decrease accuracy were used to identify oral fungal indicators of GC. RESULTS: In this study, fungal imbalance in the saliva and tongue coating was observed in the GC group. At the species level, enriched Malassezia globosa (M. globosa) and decreased Saccharomyces cerevisiae (S. cerevisiae) were observed in saliva and tongue coating samples of the GC group. Random forest analysis indicated that M. globosa in saliva and tongue coating samples could serve as biomarkers to diagnose GC. The Gini index and mean decreases in accuracy for M. globosa in saliva and tongue coating samples were the largest. In addition, M. globosa in saliva and tongue coating samples classified GC from the control with areas under the receiver operating curve (AUCs) of 0.976 and 0.846, respectively. Further ecological analysis revealed correlations between oral bacteria and fungi. CONCLUSION: For the first time, our data suggested that changes in oral fungi between GC patients and controls may help deepen our understanding of the complex spectrum of the different microbiotas involved in GC development. Although the cohort size was small, this study is the first to use 2b-RAD-M to reveal that oral M. globosa can be a fungal biomarker for detecting GC.
Subject(s)
Microbiota , Stomach Neoplasms , Humans , Tongue/microbiology , Saccharomyces cerevisiae , Bacteria , SalivaABSTRACT
BACKGROUND: This study was to explore the relationship between chronic constipation, chronic diarrhea, and frailty in older Americans. METHODS: This cross-sectional study selected a total of 4241 community-dwelling individuals aged 60 years and older from the 2005-2010 National Health and Nutrition Examination Survey. Frailty was measured using a 49-item frailty index, and a frailty index > 0.21 was defined as a frail status. Chronic constipation and chronic diarrhea were defined as the "usual or most common type of stool" by the Bristol Stool Form Scale (BSFS) Types 1 and 2 and BSFS Types 6 and 7, respectively. Weighted logistic regression analysis was used to examine the relationship between gut health and frailty status. Restricted cubic spline (RCS) curves were built to assess the association between frailty index and stool frequency. RESULTS: Frailty status was associated with higher odds of constipation in an unadjusted model; however, after further adjusting for confounding variables, the relationship between frailty status and constipation was not statistically significant. We discovered a positive correlation between the frailty status and diarrhea after adjustment for all variables. The frailty index showed a U-shaped relationship with stool frequency, and the frailty index was the smallest at a frequency of 10 stools/week. CONCLUSION: Negative associations were observed between frailty status and chronic constipation and diarrhea among older adults. Older adults who have a bowel movement frequency of about 10 times per week are the least frail. Future studies are warranted to confirm the causal relationship in this association.
Subject(s)
Frailty , Humans , United States/epidemiology , Middle Aged , Aged , Nutrition Surveys , Frailty/diagnosis , Frailty/epidemiology , Frailty/complications , Cross-Sectional Studies , Constipation/diagnosis , Constipation/epidemiology , Diarrhea/diagnosis , Diarrhea/epidemiology , Diarrhea/etiology , Frail ElderlyABSTRACT
Picrosideâ III (Pic), an iridoid glycoside derived from Picrorhiza scrophulariiflora, exhibits therapeutic potential in mending damage to the intestinal mucosa. This study aimed to explore Pic's regulatory impact on intestinal inflammation and the gut microbiota in mice with dextran sulfate sodium (DSS)-induced colitis. The findings revealed that pretreatment with Pic mitigated the DSS-induced escalation of the disease activity index (DAI), alleviated intestinal damage, and attenuated intestinal inflammation in mice. RNA-seq analysis, complemented by experimental validation, elucidated that Pic significantly hindered Akt phosphorylation in the colon tissues of colitis-afflicted mice. Furthermore, 16S rRNA sequencing demonstrated that Pic pretreatment effectively rectified microbial dysbiosis in colitis mice by elevating the abundance of Lactobacillus murinus and Lactobacillus gasseri. These observations suggest that Pic's efficacy in colitis treatment stems from its inhibition of intestinal inflammation via the suppression of the PI3K-Akt pathway and modulation of gut microbiota. This study contributes novel scientific insights into the potential application of Pic in the management of inflammatory bowel disease (IBD).
Subject(s)
Colitis , Phosphatidylinositol 3-Kinases , Mice , Animals , RNA, Ribosomal, 16S/genetics , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Transcriptome , Colitis/chemically induced , Colitis/drug therapy , Inflammation , Disease Models, AnimalABSTRACT
The investigation of chemical constituents from the rhizomes of Ruscus aculeatus resulted in the isolation of two new biphenyl derivatives, aculebiphenyls A and B (1-2), together with two known analogs (3-4). Their chemical structures were elucidated based on extensive spectroscopic interpretation and HR-ESI-MS analysis. Compounds 3-4 were isolated from the Ruscus genus for the first time. The isolated compounds were tested for anti-inflammatory activities and antibacterial activities. Compound 1 exhibited significant inhibitory effects on LPS-induced NO production and COX-2 with IC50 values of 10.8 µM and 0.4 µM. Compound 1 also significantly down-regulated the levels of inflammatory cytokines IL-1ß, IL-6, and TNF-α. Compound 1 showed moderate antibacterial activities.
Subject(s)
Ruscus , Ruscus/chemistry , Rhizome , Anti-Bacterial Agents/pharmacologyABSTRACT
Hepatocellular carcinoma (HCC) is a malignancy with a very high mortality rate. Because of its high heterogeneity, there is an urgent need to find biomarkers that accurately predict prognosis. Epithelial-mesenchymal transition (EMT) is closely associated with frequent recurrence and high mortality of HCC. Therefore, it is necessary to comprehensively analyze the prognostic value and immunological properties of EMT gene in HCC. In our study, we performed bioinformatics analysis of the TCGA and ICGC liver cancer cohorts and identified the module genes of immune-associated EMTs (iEMT) by Weighted Gene Co-Expression Network Analysis (WGCNA). Further we used machine learning (support vector machines-recursive feature elimination and Lasso) to identify three central iEMT genes (ARMC9, ADAM15 and STC2) and construct iEMT_score. Subsequently, in the training and validation cohorts, it was demonstrated that the overall survival (OS) of patients in the high iEMT_score group was worse than that of patients in the low iEMT_score group. Based on this, we have constructed a nomogram that is easy for clinicians to use. In addition, our study explored differences in pathway enrichment, immunological properties, and sensitivity to common chemotherapy and targeted drugs in different subgroups of iEMT_score. Finally, we showed through in vitro experiments that knockdown of ARMC9 could significantly inhibit the proliferation, migration and invasion of HCC cells BEL7402. Taken together, our findings suggest that iEMT_score is an excellent biomarker for predicting prognosis and provide some new insights for personalized treatment of HCC patients.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/genetics , Epithelial-Mesenchymal Transition/genetics , Liver Neoplasms/genetics , Prognosis , Machine Learning , Tumor Microenvironment/genetics , Membrane Proteins , ADAM ProteinsABSTRACT
The stopping power of energetic He ions traversing an Al film is studied by combining the time-dependent density-functional theory method with molecular dynamics simulations. We investigated the dependence of the semicore electron excitation of the Al film on the projectile's trajectory and its charge state. Our results show that for the off-channeling trajectories the semicore electrons contribute significantly to the stopping power of the Al film as the He+ ion velocity exceeds 1.0 a.u, and in contrast, it is negligible for the channeling trajectories. Most importantly, we found two unexpected effects of semicore electrons on the stopping power in helium-irradiated aluminum nanosheets, i.e., (1) the semicore electrons can contribute to the energy loss for both high and low energy projectiles under the off-channeling trajectory; (2) as the projectile velocity increases from 0.4 a.u. to 2.0 a.u. although semicore electron excitation (including transition in the target, ionization away from the target and transfer to the projectile ion) of the target atom is gradually inhibited, the influence of semicore electrons on valence electron excitation is gradually enhanced. Our finding allows us to gain new insights into the stopping of ions in metals.
ABSTRACT
Aims: To investigate the association between the number of oocytes and the polyspermy rate following in vitro fertilization (IVF) treatment. Materials and methods: 376 IVF cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol in the reproductive center of our hospital were retrospectively included in the analysis, which were divided into five groups according to the number of oocytes retrieved. Group A (78 cases):1-5 oocytes, group B (118 cases): 6-10 oocytes, group C (94 cases): 11-15 oocytes, group D (55 cases): 16-20 oocytes, group E (31 cases): ≥21 oocytes. According to polyspermy rate, 376 IVF cycles were then divided into two groups. Normal level polyspermy group (170 cases): polyspermy rate<6%, and high level polyspermy group (206 cases): polyspermy rate ≥ 6%. The variables with p < .10 in univariate analysis were incorporated into the multiple logistic regression model to control the confounding, and the effect of the number of oocytes on the increase of polyspermy rate was analyzed. Results: Multiple logistic regression analysis showed that after adjustment for confounding factor, the increase risk of polyspermy rate in group B, C, D and E was 1.763, 3.804, 2.021 and 3.208 times of that in group A respectively (OR = 1.763, p = .085; OR = 3.804, p = .001; OR = 2.021, p = .158; OR = 3.208, p = .068, respectively). Conclusion: This result demonstrated that when the oocyte number is 15 or less, the more the oocyte number, the greater the increase risk of polyspermy rate. While, there appears to be little increase risk of polyspermy rate when the oocyte number is more than 15.
Subject(s)
Fertilization in Vitro , Gonadotropin-Releasing Hormone , Oocytes , Ovulation Induction , Female , Humans , Pregnancy , Fertilization in Vitro/methods , Ovulation Induction/methods , Pregnancy Rate , Reproduction , Retrospective StudiesABSTRACT
CCL13/MCP-4 belongs to the CC chemokine family, which induces chemotaxis in many immune cells. Despite extensive research into its function in numerous disorders, a thorough analysis of CCL13 is not yet accessible. The role of CCL13 in human disorders and existing CCL13-focused therapies are outlined in this study. The function of CCL13 in rheumatic diseases, skin conditions, and cancer is comparatively well-established, and some studies also suggest that it may be involved in ocular disorders, orthopedic conditions, nasal polyps, and obesity. We also give an overview of research that found very little evidence of CCL13 in HIV, nephritis, and multiple sclerosis. Even though CCL13-mediated inflammation is frequently linked to disease pathogenesis, it's fascinating to note that in some conditions, like primary biliary cholangitis (PBC) and suicide, it might even act as a preventative measure.