Hernandonine-mediated autophagic cell death in hepatocellular carcinoma: Interplay of p53 and YAP signaling pathways.

Hepatocellular carcinoma (HCC), the primary form of liver cancer, is the third leading cause of cancer-related death globally. Hernandonine is a natural alkaloid derived from Hernandia nymphaeifolia that has been shown to exert various biological functions. In a previous study, hernandonine was shown to suppress the proliferation of several solid tumor cell lines without affecting normal human cell lines. However, little is known about the effect of hernandonine on HCC. Therefore, this study aimed to investigate the effect and mechanism of hernandonine on HCC in relation to autophagy. We found that hernandonine inhibited HCC cell growth in vitro and in vivo. In addition, hernandonine elicited autophagic cell death and DNA damage in HCC cells. RNA-seq analysis revealed that hernandonine upregulated p53 and Hippo signaling pathway-related genes in HCC cells. Small RNA interference of p53 resulted in hernandonine-induced autophagic cell death attenuation. However, inhibition of YAP sensitized HCC cells to hernandonine by increasing the autophagy induction. This is the first study to illustrate the complex involvement of p53 and YAP in the hernandonine-induced autophagic cell death in human HCC cells. Our findings provide novel evidence for the potential of hernandonine as a therapeutic agent for HCC treatment.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion.

BACKGROUND: The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM: To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS: DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS: After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION: GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers.

Objective: The leptin receptor, encoded by the LEPR gene, is involved in tumorigenesis. A potential functional variant of LEPR, rs1137101 (Gln223Arg), has been extensively investigated for its contribution to the risk of digestive system (DS) cancers, but results remain conflicting rather than conclusive. Here, we performed a case-control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk. Methods: A total of 1,727 patients with cancer (gastric/liver/colorectal: 460/480/787) and 800 healthy controls were recruited. Genotyping of rs1137101 was conducted using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and confirmed using Sanger sequencing. Twenty-four eligible studies were included in the meta-analysis. Results: After Bonferroni correction, the case-control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population. The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS, gastric, and liver cancer in the Chinese population. Conclusion: The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers (especially liver and gastric cancer) in the Chinese population.

TM-Score predicts immunotherapy efficacy and improves the performance of the machine learning prognostic model in gastric cancer.

Immunotherapy is becoming increasingly important, but the overall response rate is relatively low in the treatment of gastric cancer (GC). The application of tumor mutational burden (TMB) in predicting immunotherapy efficacy in GC patients is limited and controversial, emphasizing the importance of optimizing TMB-based patient selection. By combining TMB and major histocompatibility complex (MHC) related hub genes, we established a novel TM-Score. This score showed superior performance for immunotherapeutic selection (AUC = 0.808) compared to TMB, MSI status, and EBV status. Additionally, it predicted the prognosis of GC patients. Subsequently, a machine learning model adjusted by the TM-Score further improved the accuracy of survival prediction (AUC > 0.8). Meanwhile, we found that GC patients with low TM-Score had a higher mutation frequency, higher expression of HLA genes and immune checkpoint genes, and higher infiltration of CD8+ T cells, CD4+ helper T cells, and M1 macrophages. This suggests that TM-Score is significantly associated with tumor immunogenicity and tumor immune environment. Notably, based on the RNA-seq and scRNA-seq, it was found that AKAP5, a key component gene of TM-Score, is involved in anti-tumor immunity by promoting the infiltration of CD4+ T cells, NK cells, and myeloid cells. Additionally, siAKAP5 significantly reduced MHC-II mRNA expression in the GC cell line. In addition, our immunohistochemistry assays confirmed a positive correlation between AKAP5 and human leukocyte antigen (HLA) expression. Furthermore, AKAP5 levels were higher in patients with longer survival and those who responded to immunotherapy in GC, indicating its potential value in predicting prognosis and immunotherapy outcomes. In conclusion, TM-Score, as an optimization of TMB, is a more precise biomarker for predicting the immunotherapy efficacy of the GC population. Additionally, AKAP5 shows promise as a therapeutic target for GC.

Skin mottling score assesses peripheral tissue hypoperfusion in critically ill patients following cardiac surgery.

BACKGROUND: Skin mottling is a common manifestation of peripheral tissue hypoperfusion, and its severity can be described using the skin mottling score (SMS). This study aims to evaluate the value of the SMS in detecting peripheral tissue hypoperfusion in critically ill patients following cardiac surgery. METHODS: Critically ill patients following cardiac surgery with risk factors for tissue hypoperfusion were enrolled (n = 373). Among these overall patients, we further defined a hypotension population (n = 178) and a shock population (n = 51). Hemodynamic and perfusion parameters were recorded. The primary outcome was peripheral hypoperfusion, defined as significant prolonged capillary refill time (CRT, > 3.0 s). The characteristics and hospital mortality of patients with and without skin mottling were compared. The area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of SMS in detecting peripheral hypoperfusion. Besides, the relationships between SMS and conventional hemodynamic and perfusion parameters were investigated, and the factors most associated with the presence of skin mottling were identified. RESULTS: Of the 373-case overall population, 13 (3.5%) patients exhibited skin mottling, with SMS ranging from 1 to 5 (5, 1, 2, 2, and 3 cases, respectively). Patients with mottling had lower mean arterial pressure, higher vasopressor dose, less urine output (UO), higher CRT, lactate levels and hospital mortality (84.6% vs. 12.2%, p < 0.001). The occurrences of skin mottling were higher in hypotension population and shock population, reaching 5.6% and 15.7%, respectively. The AUROC for SMS to identify peripheral hypoperfusion was 0.64, 0.68, and 0.81 in the overall, hypotension, and shock populations, respectively. The optimal SMS threshold was 1, which corresponded to specificities of 98, 97 and 91 and sensitivities of 29, 38 and 67 in the three populations (overall, hypotension and shock). The correlation of UO, lactate, CRT and vasopressor dose with SMS was significant, among them, UO and CRT were identified as two major factors associated with the presence of skin mottling. CONCLUSION: In critically ill patients following cardiac surgery, SMS is a very specific yet less sensitive parameter for detecting peripheral tissue hypoperfusion.

Knowledge domains and emerging trends in immune-related adverse events from immune checkpoint inhibitors: A bibliometrics and visualized analysis.

Objective: The primary objective of this paper is to investigate the research hotspots and future trends of immune-related adverse events induced by immune checkpoint inhibitors, offering valuable insights for researchers in this field. Methodology: Using the visual analysis software, this study conducted quantitative statistics and visualization research on the relevant literature concerning immune-related adverse events caused by immune checkpoint inhibitors in the Web of Science Core Collection Database. By evaluating the publication trends, countries, institutions, keywords, research status, cited documents, and document co-citations, among several others, the discussion revolved around the hot spots and future development trends in this field and provided references for future research. Findings and conclusions: A total of 514 English articles were included, and the top three countries in the research field at the time of this study were the United States, Japan, and China. More specifically, the University of Texas MD Anderson Cancer Center, Dana-Farber Cancer Institute, and Massachusetts General Hospital have been the top three research institutes with more than 10 publications. The frequency of keyword use linked to immune-related adverse events caused by immune checkpoint inhibitors in literature research has been steadily growing over the years. Additionally, the research with respect to the disease focuses on melanoma, cell lung cancer, hepatocellular carcinoma, and breast cancer. In the context of drugs, cancer-related research has mainly focused on the combined use of nivolumab, pembrolizumab, ipilimumab, and immune checkpoint inhibitors. Meanwhile, research on adverse events has delved into the immune checkpoint inhibitors causing vitiligo, thyroid dysfunction, pancreatitis, cholangitis, and rheumatism. Related studies cover acute arthritis, myositis, acute kidney injury, as well as the combination therapy of immune checkpoint inhibitors and docetaxel, management of irAEs in cancer immunotherapy, and biomarkers of immune adverse reactions of immune checkpoint inhibitors. Finally, case report studies of immune adverse reactions caused by immune checkpoint inhibitors could serve as research hotspots in the future.

Artificial intelligence in the risk prediction models of cardiovascular disease and development of an independent validation screening tool: a systematic review.

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.

Fabrication of levofloxacin-loaded porcine acellular dermal matrix hydrogel and functional assessment in urinary tract infection.

Bacterial cystitis, a commonly occurring urinary tract infection (UTI), is renowned for its extensive prevalence and tendency to recur. Despite the extensive utilization of levofloxacin as a conventional therapeutic approach for bacterial cystitis, its effectiveness is impeded by adverse toxic effects, drug resistance concerns, and its influence on the gut microbiota. This study introduces Lev@PADM, a hydrogel with antibacterial properties that demonstrates efficacy in the treatment of bacterial cystitis. Lev@PADM is produced by combining levofloxacin with decellularized porcine acellular dermal matrix hydrogel and exhibits remarkable biocompatibility. Lev@PADM demonstrates excellent stability as a hydrogel at body temperature, enabling direct administration to the site of infection through intravesical injection. This localized delivery route circumvents the systemic circulation of levofloxacin, resulting in a swift and substantial elevation of the antimicrobial agent's concentration specifically at the site of infection. The in vivo experimental findings provide evidence that Lev@PADM effectively prolongs the duration of levofloxacin's action, impedes the retention and invasion of E.coli in the urinary tract, diminishes the infiltration of innate immune cells into infected tissues, and simultaneously preserves the composition of the intestinal microbiota. These results indicate that, in comparison to the exclusive administration of levofloxacin, Lev@PADM offers notable benefits in terms of preserving the integrity of the bladder epithelial barrier and suppressing the recurrence of urinary tract infections.

A Comparative Study of the Effects of Electronic Cigarette and Traditional Cigarette on the Pulmonary Functions of C57BL/6 Male Mice.

INTRODUCTION: Electronic cigarettes (E-cigs) are in a controversial state. Although E-cig aerosol generally contains fewer harmful substances than smoke from burned traditional cigarettes, aerosol along with other compounds of the E-cigs may also affect lung functions and promote the development of lung-related diseases. We investigated the effects of E-cig on the pulmonary functions of male C57BL/6 mice and reveal the potential underlying mechanisms. METHODS: A total of 60 male C57BL/6 mice were randomly divided into four groups. They were exposed to fresh-air, traditional cigarette smoke, E-cig vapor with 12 mg/mL of nicotine, and E-cig with no nicotine for 8 weeks. Lung functions were evaluated by using quantitative analysis of the whole body plethysmograph, FlexiVent system, lung tissue histological and morphometric analysis, and RT-PCR analysis of mRNA expression of inflammation-related genes. In addition, the effects of nicotine and acrolein on the survival rate and DNA damage were investigated using cultured human alveolar basal epithelial cells. RESULTS: Exposure to E-cig vapor led to significant changes in lung functions and structures including the rupture of the alveolar cavity and enlarged alveolar space. The pathological changes were also accompanied by increased expression of interleukin-6 and tumor necrosis factor-α. CONCLUSIONS: The findings of the present study indicate that the safety of E-cig should be further evaluated. IMPLICATIONS: Some people currently believe that using nicotine-free E-cigs is a safe way to smoke. However, our research shows that E-cigs can cause lung damage regardless of whether they contain nicotine.

Furosemide Responsiveness Predicts Acute Kidney Injury Progression After Cardiac Surgery.

BACKGROUND: As patients with acute kidney injury (AKI) progress to a higher stage, the risk for poor outcomes dramatically rises. Early identification of patients at high risk for AKI progression remains a major challenge. This study aimed to evaluate the value of furosemide responsiveness (FR) for predicting AKI progression in patients with initial mild and moderate AKI after cardiac surgery. METHODS: We performed 2 separate exploratory analyses. The Zhongshan cohort was a single-center, prospective, observational cohort, whereas the Beth Israel Deaconess Medical Center cohort was a single-center, retrospective cohort. We calculated 2 FR parameters for each patient, namely the FR index and modified FR index, defined as 2-hour urine output divided by furosemide dose (FR index, mL/mg/2 h) and by furosemide dose and body weight (modified FR index, mL/[mg·kg]/2 h), respectively. The primary outcome was AKI progression within 7 days. RESULTS: AKI progression occurred in 80 (16.0%) and 359 (11.3%) patients in the Zhongshan and Beth Israel Deaconess Medical Center cohorts, respectively. All FR parameters (considered continuously or in quartiles) were inversely associated with risk of AKI progression in both cohorts (all adjusted P < .01). The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models involving C-index, net reclassification improvement, and integrated discrimination improvement index in both cohorts (all P < .01). CONCLUSIONS: FR parameters were inversely associated with risk of AKI progression in patients with mild and moderate AKI after cardiac surgery. The addition of FR parameters significantly improved prediction for AKI progression based on baseline clinical models.

Correlation between maximum heart distance and thoracic diameter changes and diaphragmatic descent in left-sided breast cancer patients during deep inspiration breath-hold (DIBH).

BACKGROUND: Cardioprotection is valued in radiotherapy for patients with left-sided breast cancer. Deep inspiration breath-hold (DIBH) technique can achieve cardioprotection well. However, during DIBH, the extent to which the heart enters the radiation field is affected by the movement of the thorax and diaphragm. The aim of this study was to analyze the correlation between the maximum distance of the heart entering the field (maximum heart distance, MHD) and thoracic diameter changes and diaphragmatic descent in left-sided breast cancer patients during DIBH. PATIENTS AND METHODS: Ninety-eight patients with left-sided breast cancer were included in this retrospective study. They performed simulation in Sentinel-guided DIBH, and two sets of CT images were collected under both free breathing (FB) and DIBH, and diaphragm positions, anteroposterior thoracic diameter (ATD), transverse thoracic diameter (TTD), gating window level (GWL), and MHD were measured, and the change (Δ) of each parameter in DIBH relative to that in FB were calculated. Pearson or Spearman test were used to analyze the correlation between ΔMHD and the changes in other parameters. RESULTS: For all patients with DIBH, the average of ΔMHD was -8.3 mm, and the average of ΔATD and ΔTTD were 11.0 and 8.6 mm, and the median of both left diaphragmatic descent (LDD) and right diaphragmatic descent (RDD) were 35.0 mm, and the median of GWL was 11.1 mm. The correlation coefficients between MHD decrease (ΔMHD) and LDD, RDD, and ΔTTD were -0.430 (p = 0.000), -0.592 (p = 0.000) and 0.208 (p = 0.040), respectively, but not significantly correlated with ΔATD or GWL. CONCLUSIONS: The MHD decrease showed a moderate correlation with diaphragmatic descent In Sentinel-guided DIBH for patients with left-sided breast cancer, while there was a weak or no correlation with thoracic diameter changes or GWL. Abdominal breathing can lower diaphragm more and may be more beneficial to the heart stay away from tangential field.

Hotspots and future trends of autophagy in Traditional Chinese Medicine: A Bibliometric analysis.

Objective: To discuss the hotspots and future trends of autophagy in traditional Chinese medicine (TCM) and provide a reference for researchers in this field. Method: Using visual analysis tools, metrological statistics and visual research on the pertinent literature in the area of autophagy use in TCM were undertaken in the core collection database of the Web of Science. By examining the authors, keywords, research circumstances, research hotspots, and trends of linked research, the use of autophagy in TCM was investigated. Results and Conclusions: A total of 916 studies were included, among which Beijing University Chinese Medicine was the largest number of advantageous research institutions, followed by Shanghai University Traditional Chinese Medicine and Guangzhou University Chinese Medicine.The keywords of literature research primarily comprise apoptosis, activation, inhibition, pathway, mechanism, oxidative stress, proliferation, NF-κB, cancer, mtor, etc. At present, the research on autophagy in the field of TCM is increasing on a year-to-year basis. The research has focused on the role played by TCM in malignant tumors, atherosclerosis, Alzheimer's disease through autophagy, and the regulation of autophagy signaling pathways (e.g., PI3K/AKT/mTOR signaling pathway, TLR4 signaling pathway,nrf2 signaling pathway and NF-κB signaling pathway). In the future, the therapeutic effect of TCM on chemotherapy-resistant tumor cells through autophagy pathway, the role of TCM mediating mitophagy and activating autophagy function, and the therapeutic effect of TCM components represented by luteolin on tumors, asthma, myocardial injury and other diseases through autophagy mechanism will be the research hotspots in the future.

Critical role of heme oxygenase-1 in chaetoglobosin A by triggering reactive oxygen species mediated mitochondrial apoptosis in colorectal cancer.

The incidence rate of colorectal cancer (CRC) has been increasing and poses severe threats to human health worldwide and developing effective treatment strategies remains an urgent task. In this study, Chaetoglobosin A (ChA), an endophytic fungal metabolite from the medicinal herb-derived fungus Chaetomium globosum Km1126, was identified as a potent and selective antitumor agent in human CRC. ChA induced growth inhibition of CRC cells in a concentration-dependent manner but did not impair the viability of normal colon cells. ChA triggered mitochondrial intrinsic and caspase-dependent apoptotic cell death. In addition, apoptosis antibody array analysis revealed that expression of Heme oxygenase-1 (HO-1) was significantly increased by ChA. Inhibition of HO-1 increased the sensitivity of CRC cells to ChA, suggesting HO-1 may play a protective role in ChA-mediated cell death. ChA induced cell apoptosis via the induction of reactive oxygen species (ROS) and ROS scavenger (NAC) prevented ChA-induced cell death, mitochondrial dysfunction, and HO-1 activation. ChA promoted the activation of c-Jun N-terminal kinase (JNK), and co-administration of JNK inhibitor or siRNA markedly reversed ChA-mediated apoptosis. ChA significantly decreased the tumor growth without eliciting any organ toxicity or affecting the body weight of the CRC xenograft mice. This is the first study to demonstrate that ChA exhibits promising anti-cancer properties against human CRC both in vitro and in vivo. ChA is a potential therapeutic agent worthy of further development in clinical trials for cancer treatment.

The medial preoptic area mediates depressive-like behaviors induced by ovarian hormone withdrawal through distinct GABAergic projections.

Fluctuations in reproductive hormone levels are associated with mood disruptions in women, such as in postpartum and perimenopausal depression. However, the neural circuit mechanisms remain unclear. Here we report that medial preoptic area (MPOA) GABAergic neurons mediate multifaceted depressive-like behaviors in female mice after ovarian hormone withdrawal (HW), which can be attributed to downregulation of activity in Esr1 (estrogen receptor-1)-expressing GABAergic neurons. Enhancing activity of these neurons ameliorates depressive-like behaviors in HW-treated mice, whereas reducing their activity results in expression of these behaviors. Two separate subpopulations mediate different symptoms: a subpopulation projecting to the ventral tegmental area (VTA) mediates anhedonia and another projecting to the periaqueductal gray mediates immobility. These projections enhance activity of dopaminergic neurons in the VTA and serotonergic neurons in the dorsal raphe, respectively, with increased release of dopamine and serotonin, possibly through disinhibition mechanisms. Thus, the MPOA is a hub that mediates depressive-like behaviors resulting from transitions in reproductive hormone levels.

Space Charge Characteristics and Breakdown Properties of Nanostructured SiO2/PP Composites.

Polypropylene (PP) has gained attention in the industry as an environmentally friendly material. However, its electrical properties are compromised due to space charge accumulation during operation, limiting its application in high-voltage DC cable insulation. This study investigates the effect and mechanism of SiO2 with a DDS surface hydrophobic treatment on space charge suppression and the electrical properties of PP composites. The PP matrix was doped with SiO2 nanostructures, both with a DDS surface hydrophobic treatment and untreated as a control group. The functional group structure and dispersion of nanostructured SiO2 in the matrix were characterized. The findings reveal that the incorporation of SiO2 nanostructures effectively mitigates charge accumulation in PP composites. However, a high concentration of unsurfaced nanostructures tends to agglomerate, resulting in inadequate space charge suppression and a diminished DC breakdown field strength. Nonetheless, surface treatment improves the dispersion of SiO2 within the matrix. Notably, the composite containing 1.0 wt% of surface hydrophobic SiO2 exhibits the least space charge accumulation. Compared to the base material PP, the average charge density is reduced by 83.9% after the 1800 s short-circuit discharges. Moreover, its DC breakdown field strength reaches 3.45 × 108 V/m, surpassing pure PP by 19.4% and untreated SiO2/PP composites of the same proportion by 24.0%.

Degradation of Aflatoxin B1 in Peanut Oil by Ultraviolet-LED Cold-Light Irradiation and Structure Elucidation of the Degradation Products.

This study aimed to determine the efficiency of ultraviolet (UV)-LED cold light treatment on the degradation of aflatoxin (AF)B1 in peanut oils. The peanut oil samples obtained from different places in China and abroad were determined for AFB1 degradation efficiency of the UV-LED cold-light irradiation method. The degradation products were analyzed by ultra-high performance liquid chromatography coupled to quadrupole orbitrap high-resolution mass spectrometry (UPLC-Q-Exactive MS). The results indicated that the AFB1 content in all peanut oil samples decreased rapidly after 5 min of irradiation. Four main photodegradation products (C18H16O7, C17H14O7, C17H14O7, and C17H14O8) were identified using the established LC-MS method. Their chemical structures were postulated based on the LC-MS data. Also, the degradation pathways were proposed based on the data obtained. Oxidation and reduction reactions were mainly responsible for AFB1-decomposition. The reactions occurred at the furan and lactone rings. These findings demonstrated that UV-LED cold-light irradiation was an effective method for treating AFB1- contaminated peanut oil.

Transjugular Transcatheter Tricuspid Valve Implantation of LuX-Valve Bioprosthesis in a Preclinical Model.

The purpose of this preclinical study in a sheep model was to confirm the feasibility and safety of the LuX-Valve transjugular tricuspid valve (TV) replacement apparatus and to optimize the implantation procedure before beginning first-in-man study. The LuX-Valve was implanted in a sheep model (n = 8) via transjugular approach. Six of eight sheep underwent successful implantation procedure on beating heart. The first two sheep died during the prostheses deployment. In the remaining 6 sheep that survived, postoperative echocardiography results showed there was no paravalvular leakage (PVL) and central tricuspid regurgitation in 5 animals, whereas 1 animal had mild PVL. The mean transvalvular gradient was 1.1 ± 0.9 mm Hg at the 4-week follow-up. No right ventricular outflow tract (RVOT) obstruction, device malposition, pericardial effusion, coronary artery compression, or arrhythmias were observed. This technology may be a promising alternative for TR patients who are at high risk for open-heart surgery. Transjugular tricuspid valved-stent implantation. a Transjugular tricuspid valve replacement in a sheep model. b and c Valved stent. d, e, and f Schematic depiction of the implantation procedure.

Pulmonary and tricuspid regurgitation after Tetralogy of Fallot repair: A case report.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common congenital heart defects, and surgery is the primary treatment. There are no precise guidelines on the treatment protocol for tricuspid regurgitation (TR) as a common complication of TOF repair. The timing for treatment in patients presenting with valve regurgitation after TOF repair is often difficult to determine. Here, we report the first case of sequential treatment of pulmonary and TR using interventional therapy. CASE SUMMARY: We present the case of a 52-year-old female patient, who had a history of TOF repair at a young age. A few years later, the patient presented with pulmonary and tricuspid regurgitation. The symptoms persisted and TR worsened following percutaneous pulmonary valve implantation. Preoperative testing revealed that the patient's disease had advanced to an intermediate to advanced stage and that her general health was precarious. Because open-heart surgery was not an option for the patient, transcatheter tricuspid valve replacement was suggested. This procedure was successful, and the patient recovered fully without any adverse effects. This case report may serve as a useful resource for planning future treatments. CONCLUSION: Treatment of both valves should be considered in patients with tricuspid and pulmonary regurgitations following TOF repair. The interventional strategy could be an alternative for patients with poor general health.

Cryptocaryone induces apoptosis in human hepatocellular carcinoma cells by inhibiting aerobic glycolysis through Akt and c-Src signaling pathways.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, with the second highest mortality rate in all cancer. Energy reprogramming is one of the hallmarks of cancer, and emerging evidence showed that targeting glycolysis is a promising strategy for HCC treatment. Cryptocaryone has been shown to display promising anti-cancer activity against numerous types of cancer. Previous study also indicated that cryptocaryone induces cytotoxicity by inhibiting glucose transport in cancer cells, but the detailed mechanism still needs to be elucidated. Therefore, this study aimed to investigate the relationship between the anti-cancer effect and glycolytic metabolism of cryptocaryone in human HCC cells. In this study, we found that cryptocaryone potently induced growth inhibition by apoptotic cell death in HCC cells. Cryptocaryone also suppressed the ATP synthesis, lactate production and glycolytic capacity of HCC cells. Mechanistic investigations showed that phosphorylation of Akt and c-Src, as well as the expression of HK1 were impeded by cryptocaryone. Moreover, cryptocaryone markedly increased the expression level of transcription factor FoxO1. Importantly, clinical database analysis confirmed the negative correlation between HK1 and FoxO1. High expression levels of HK-1 were positively correlated with poorer survival in patients with HCCs. These results suggest that cryptocaryone may promote cell apoptosis by inhibiting FoxO1-mediated aerobic glycolysis through Akt and c-Src signaling cascades in human HCC cells. This is the first study to indicate that cryptocaryone exerts anti-cancer property against human HCC cells. Cryptocaryone is a potential natural product worthy of further development into a promising candidate for HCC treatment.

Honokiol Reduces Mitochondrial Dysfunction and Inhibits Apoptosis of Nerve Cells in Rats with Traumatic Brain Injury by Activating the Mitochondrial Unfolded Protein Response.

This study was designed to determine the effects and underlying mechanism of honokiol (HNK) on traumatic brain injury (TBI). A rat TBI model was constructed using the modified Feeney free-fall percussion method and treatment with HNK via intraperitoneal injection. The brain tissues of the rats in each group were assessed using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay to detect the level of neuronal apoptosis. Western blots were used to detect the expression levels of apoptosis-related proteins (Bcl-2 and Bax), and ELISAs were used to measure the levels of pro-inflammatory cytokines (IL-18 and IL-1ß) and the activity of caspase-1. In addition, the mitochondrial membrane potential, reactive oxygen species (ROS), and adenosine 5'-triphosphate (ATP) were also measured. Western blots and qRT-PCRs were used to determine the relative expression levels of the mitochondrial unfolded protein response (UPRmt)-related proteins and mRNAs. Based on the experimental results, treatment with HNK was associated with a decrease in the number of TUNEL-positive cells, downregulated Bax expression levels, elevated Bcl-2 expression levels, and inhibition of neuronal apoptosis in the brain tissue of TBI rats. HNK also suppressed neuroinflammation by decreasing IL-1ß and IL-18 levels and caspase-1 activity. Additionally, HNK lowered the mitochondrial membrane potential and ROS levels, increased ATP levels, and improved mitochondrial dysfunction in neural cells. Furthermore, in the investigation of the mechanism of HNK on TBI, we observed that HNK could activate UPRmt by upregulating the mRNA and protein expression levels of HSPA9, CLPP, and HSP60 in the brain tissues of TBI rats. Collectively, HNK reduced mitochondrial dysfunction, inhibited the apoptosis of nerve cells, and attenuated inflammation in the brains of TBI rats. The protective effect of HNK may be achieved through the activation of UPRmt.