Bioscience trends最新文献

Coronary artery calcification (CAC) is an early marker for atherosclerosis and is mainly induced by the osteoblast-like phenotype conversion of vascular smooth muscle cells (VSMCs). Recent reports indicate that NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis plays a significant role in the calcification of vascular smooth muscle cells (VSMCs), making it a promising target for treating calcific aortic valve disease (CAC). Ligustrazine, or tetramethylpyrazine (TMP), has been found effective in various cardiovascular and cerebrovascular diseases and is suggested to inhibit NLRP3-mediated pyroptosis. However, the function of TMP in CAC is unknown. Herein, influences of TMP on β-glycerophosphate (β-GP)-stimulated VSMCs and OPG^-/- mice were explored. Mouse Aortic Vascular Smooth Muscle (MOVAS-1) cells were stimulated by β-GP with si- caspase-3, si- Gasdermin E (GSDME) or TMP. Increased calcification, reactive oxygen species (ROS) level, Interleukin-1beta (IL-1β) and Interleukin-18 (IL-18) levels, lactate dehydrogenase (LDH) release, enhanced apoptosis, and activated cysteine-aspartic acid protease-3 (caspase-3)/GSDME signaling were observed in β-GP-stimulated MOVAS-1 cells, which was sharply alleviated by si-caspase-3, si-GSDME or TMP. Furthermore, the impact of TMP on the β-GP-induced calcification and injury in MOVAS-1 cells was abolished by raptinal, an activator of caspase-3. Subsequently, OPG^-/- mice were dosed with TMP or TMP combined with raptinal. Calcium deposition, increased nodules, elevated IL-1β and IL-18 levels, upregulated CASP3 and actin alpha 2, smooth muscle (ACTA2), and activated caspase-3/GSDME signaling in OPG^-/- mice were markedly alleviated by TMP, which were notably reversed by the co-administration of raptinal. Collectively, TMP mitigated CAC by inhibiting caspase-3/GSDME mediated pyroptosis.

Biliary tract tumors (BTC) account for about 3% of all digestive system tumors, with rising incidence and limited treatment options, particularly for advanced stages, underscoring the need for innovative therapies. This retrospective cohort study evaluated the safety and efficacy of a novel regimen combining hepatic artery infusion chemotherapy with 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX-HAIC) alongside lenvatinib and programmed cell death protein-1 (PD-1) inhibitors (mFOLFOX-HAIC+lenvatinib+PD-1i) compared to standard regimens of gemcitabine plus cisplatin, gemcitabine plus S1, or gemcitabine plus oxaliplatin (GC/GS/GEMOX) in advanced BTC patients treated from March 2019 to November 2023. A total of 89 patients were analyzed, with 55 receiving hepatic arterial infusion chemotherapy and 34 receiving the GC/GS/GEMOX regimens. Among these, 23 patients were in the mFOLFOX-HAIC+lenvatinib+PD-1i group, while 24 were in the GC/GS/GEMOX group. The median progression-free survival (mPFS) for the mFOLFOX-HAIC+lenvatinib+PD-1i group was 15 months compared to 6 months for the GC/GS/GEMOX group. Similarly, the median overall survival (mOS) was 20 months for the mFOLFOXHAIC+lenvatinib+PD-1i group versus 13 months for the GC/GS/GEMOX group. The objective response rate (ORR) and disease control rate (DCR) for the mFOLFOX-HAIC+lenvatinib+PD-1i group were 48.5% and 87.0%, respectively, both significantly higher than those observed in the GC/GS/GEMOX group at three months of treatment. The incidence of adverse events (AEs) was similar between the mFOLFOX-HAIC+lenvatinib+PD-1i group and the GC/GS/GEMOX group, at 86.5% and 84.2%, respectively, with no statistically significant difference in complication rates. Overall, mFOLFOX-HAIC+lenvatinib+PD-1i appears to be a safe and well-tolerated treatment for advanced BTC, demonstrating superior mPFS and mOS compared to standard regimens.

Intrahepatic bile duct mucinous adenocarcinoma (IHBDMAC) is a rare pathological subtype of intrahepatic cholangiocarcinoma (IHCC), and its tumor biological features and survival outcomes have rarely been explored, especially when compared to the most common subtype, intrahepatic bile duct adenocarcinoma (IHBDAC). Therefore, the aim of this study was to explore the clinical features and survival outcomes of IHBDAC and IHBDMAC using the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2021. A total of 1,126 patients were included, with 1,083 diagnosed with IHBDAC and 43 diagnosed with IHBDMAC. Patients with IHBDMAC presented with a more advanced T stage (55.8% vs. 36.9%, P = 0.012) and higher rate of lymph node metastasis (37.2% vs. 24.9%, P = 0.070). Cox regression identified advanced T stage, lymph node metastasis, and distant metastasis as poor survival predictors, while chemotherapy and surgery were protective factors. Survival analyses revealed significantly worse overall survival (OS) and cancer-specific survival (CSS) for IHBDMAC compared to IHBDAC (P < 0.05). Even after matching, patients with IHBDMAC still had a worse prognosis than those with IHBDAC. These findings highlight the aggressive nature of IHBDMAC and the need for tailored therapeutic strategies. Future research should focus on prospective studies and molecular insights to develop targeted treatments for IHBDMAC.

Differences in social capital have been shown to impact psychological distress in cancer patients, but few studies have examined the relationship between social capital and the distress thermometer (DT) in breast cancer patients who have undergone modified radical surgery. To fill this research gap, our study aimed to investigate the association between social capital and the DT among breast cancer patients who underwent modified radical surgery in Anhui Province, China. This cross-sectional study used multi-stage stratified random sampling. Data on demographic characteristics, eight dimensions of social capital, and the DT were collected using a questionnaire. Logistic regression models were subsequently utilized to assess the relationship between social capital and DT, adjusting for confounding factors. A total of 253 participants were included in the final analysis. Results indicated that individuals with higher levels of social capital, including participation in the local community (OR = 3.437; 95% CI: 1.734-6.814), social agency or proactivity in a social context (OR = 69.700; 95% CI: 20.142-241.195), feelings of trust and safety (OR = 26.287; 95% CI: 7.646-90.374), neighborhood connections (OR = 7.022; 95% CI: 3.020-16.236), family and friend connections (OR = 59.315; 95% CI: 17.182-204.760), tolerance of diversity (OR = 9.785; 95% CI: 4.736-20.216), value of life (OR = 65.142; 95% CI: 19.994-212.242), and work connections (OR = 31.842; 95% CI: 12.612-80.397), had higher odds of reporting poor DT scores compared to those with lower levels of social capital. These findings indicate an association between social capital and DT scores in breast cancer patients who have undergone modified radical surgery, suggesting that social capital may play a crucial role in alleviating psychological distress within this community.

Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.

Genetic screening of newborns for deafness plays an important role in elucidating the etiology of deafness, diagnosing it early, and intervening in it. Genetic screening of newborns has been conducted for 11 years in Beijing. It started with a chip to screen for 9 variants of 4 genes in 2012; the chip screened for 15 variants of those genes in 2018, and it now screens for 23 variants of those genes. In the current study, a comparative analysis of three screening protocols and follow-up for infants with pathogenic variants was performed. The rates of detection and hearing test results of infants with pathogenic variants were analyzed. Subjects were 493,821 infants born at 122 maternal and child care centers in Beijing from April 2012 to August 2023. Positivity increased from 4.599% for the chip to screen for 9 variants to 4.971% for the chip to screen for 15 variants, and further to 11.489% for the chip to screen for 23 variants. The carrier frequency of the GJB2 gene increased from 2.489% for the chip to screen for 9 variants and 2.422% for the chip to screen for 15 variants to 9.055% for the chip to screen for 23 variants. The carrier frequency of the SLC26A4 gene increased from 1.621% for the chip to screen for 9 variants to 2.015% for the chip to screen for 15 variants and then to 2.151% for the chip to screen for 23 variants. According to the chip to screen for 9 variants and the chip to screen for 15 variants, the most frequent mutant allele was c.235delC. According to the chip to screen for 23 variants, the most frequent mutant allele was c.109G>A. The chip to screen for 15 variants was used to screen 66.67% (14/21) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. The chip to screen for 23 variants was used to screen 92.98% (53/57) of newborns with biallelic variants in the GJB2 gene (52 cases were biallelic c.109G>A) and 25% (1/4) of newborns with biallelic variants in the SLC26A4 gene for newly added mutations. Among the infants with pathogenic variants (biallelic variants in GJB2 or SLC26A4), 20.66% (25/121) currently have normal hearing. In addition, 34.62% (9/26) of newborns who passed the hearing screening were diagnosed with hearing loss. Findings indicate that a growing number of newborns have benefited, and especially in the early identification of potential late-onset hearing loss, as the number of screening sites has increased. Conducting long-term audiological monitoring for biallelic variants in individuals with normal hearing is of paramount significance.

Cells routinely utilize the unfolded protein response (UPR) to alleviate endoplasmic reticulum (ER)-stress or trigger about apoptotic death under extreme ER-stress conditions. Tumor cells are subjected to persistent ER-stress due to their crowded microenvironment, but can maintain hyperactive proliferation under most stressful conditions. Therefore, understanding strategies employed by cancer cells to escape from UPR-related apoptosis has important medical implications. SEC24 homolog C (SEC24C) was found decreased in later colorectal cancer (CRC) stages, but its exact role in response to ER-stress and activation of UPR in hepatocellular carcinoma (HCC) remains to be elucidated. Here, we have identified the downregulation of SEC24C in human HCC sample and its suppressive role in regulating HCC proliferation and chemoresistance. Mechanistically, SEC24C was found to interact with eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3 or PERK) and activate the downstream UPR-related apoptosis. During this process, SEC24C was observed to be anchored in nucleus under normal condition but responded immediately to ER-stress and could subsequently translocate to the ER. Furthermore, overexpression of SEC24C significantly augmented the efficacy of bortezomib in HCC treatment. In conclusion, our findings revealed a novel role of SEC24C in regulating HCC proliferation and chemoresistance by modulating UPR activation.

Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model.

Congenital birth defects (CBD) play a significant role in causing child mortality globally. The incidence and mortality of CBD vary widely across countries, and the underlying causes for this divergence remain incompletely comprehended. We conducted an analysis to investigate the relationship between the incidence and mortality of CBD in 189 countries and their Human Development Index (HDI). In this study, CBD data from 189 countries was used from the Global Burden of Diseases Study (GBD) 2019, and HDI data was collected for the same countries. Later, the relationship between CBD and HDI was analyzed, and the impact of gross national income (GNI) per capita, expected years of schooling, mean years of schooling and life expectancy at birth was quantified using principal component regression. The age-standardized incidence rate (ASIR) varied between 66.57 to 202.24 per 100,000, with a 95% uncertainty interval (UI) of 57.20-77.51 and 165.87-241.48 respectively. The age-standardized mortality rate (ASMR) also showed a rang from 1.38 to 26.53 (14.03-39.90) per 100,000, with the 95%UI of 0.91-2.09 and 14.03-39.90 respectively. Both the incidence and mortality rates of CBD decreased with the increased HDI (incidence: r = -0.38, p < 0.001, mortality: r = -0.77, p < 0.001). Our investigation revealed significant variations in the incidence and mortality of CBD among countries with different development levels. In conclusion, the global incidence and mortality of CBD vary significantly among countries, possibly due to differences in the accessibility of health services.

The prognostic significance of the signet-ring cell component in gallbladder carcinoma (GBC) has not been systematically evaluated. The aim of this study was to assess the similarities and differences between gallbladder signet-ring cell carcinoma (GBSRCA) and gallbladder adenocarcinoma (GBAC) in terms of clinicopathological features and long-term survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed 6,612 patients diagnosed with gallbladder cancer between 2000 and 2021. The cohort included 147 patients with GBSRCA and 6,465 with GBAC. Patients with GBSRCA were significantly younger, with 33.3% being age 60 or younger compared to 23.9% of patients with GBAC (p = 0.009). There was a higher proportion of females in the GBSRCA group (77.6%) compared to the GBAC group (70.1%, p = 0.049). GBSRCA was associated with a more advanced tumor stage (T3-T4: 56.5% vs. 44.4%, P = 0.004), higher rates of lymph node metastasis (43.5% vs. 28.0%, P < 0.001), and poorer differentiation status (poorly to undifferentiated: 80.3% vs. 29.7%, P < 0.001). Survival analysis revealed that patients with GBSRCA had significantly worse overall survival (OS) and cancer-specific survival (CSS) compared to patients with GBAC (p < 0.001). GBSRCA was an independent prognostic factor for OS (P = 0.001) in the entire cohort, while the T stage and N stage were independent prognostic factors for OS and CSS in patients with GBSRCA. Even after propensity score matching, patients with GBSRCA still had a poorer prognosis.