A metabolomics perspective reveals the mechanism of the uric acid-lowering effect of Prunus salicina Lindl. cv. "furong" polyphenols in hypoxanthine and potassium oxybate-induced hyperuricemic mice.

The incidence of hyperuricemia (HUA) shows a gradually increasing trend towards affecting younger individuals, and it can significantly harm the overall health status of the body. Based on a metabolomics perspective, this study reveals the mechanism of the uric acid-lowering action of Prunus salicina Lindl. cv. "furong" polyphenols (PSLP) on a hyperuricemia mouse model induced by hypoxanthine and potassium oxybutyrate. The results demonstrate that PSLP comprise an effective treatment strategy for reducing the levels of serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) in HUA mice (p < 0.05), wherein the maximum decrease rates are up to 44.50%, 29.46%, and 32.95%, respectively. PSLP are observed to exert a pronounced inhibitory effect on the activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the livers of HUA mice, with reductions of up to 16.36% and 20.13%, respectively. These findings illustrate that PSLP exert a significant uric acid-lowering effect. Subsequent metabolomic analysis of mouse serum identified 28 potential biomarkers for hyperuricemia, whose levels were markedly diminished by PSLP. This process involved alterations in purine, glycine, the pentose phosphate pathway, and galactose metabolism. Twenty-eight potential biomarkers were identified for hyperuricemia by subsequent metabolomic analysis of mouse serum, whose levels were markedly reversed by PSLP intervention. The regulation of HUA by PSLP involved alterations in purine metabolism, glycerolipid metabolism, the pentose phosphate pathway, and galactose metabolism. The mechanism of PSLP ameliorated hyperuricemia might be attributed to reduction of the level of the uric acid precursor ribose-5-phosphate in the pentose phosphate pathway, the inhibition of the activities of uric acid synthase XOD and ADA in purine metabolism, and reduction of the synthesis of the end product uric acid. This study provides a theoretical basis for the development of functional foods based on PSLP, which can potentially reduce uric acid levels.

A sarcopenia screening test predicts mortality among hospitalized cancer patients.

This study investigated the ability of a sarcopenia screening test to predict mortality among cancer inpatients. We conducted a prospective study of patients admitted to the oncology ward of a teaching hospital in southern Taiwan. Over a 5-month period, 82 patients were enrolled for evaluation and were followed for 3 years. All participants received a comprehensive assessment at the time of admission, including Eastern Cooperative Oncology Group (ECOG) performance status, cognitive ability, nutrition index, body mass index, and short physical performance battery (SPPB). Age, ECOG performance status, dementia, SPPB score, and albumin level were associated with sarcopenia. Of the enrolled participants, 53 (64.6%) were diagnosed with sarcopenia. Patients with sarcopenia were associated with worse overall survival (OS) than patients without sarcopenia (28.8% vs. 82%, p = 0.01). Metastasis (hazard ratio [HR]: 5.166; 95% confidence interval [CI]: 1.358-19.656) and albumin level (HR: 4.346; 95% CI: 1.493-12.654) were independent and significant predictors of OS for the whole study population. Age was a predictor of 2-year all-cause mortality among patients aged ≥65 years but not among those aged <65 years (OS: 25.6% vs. 100%, p = 0.04). To summarize, the sarcopenia screening results were found to predict OS and all-cause mortality and may be helpful for patient stratification during in-hospital care.

The Mechanism of 540 nm Green Light in Promoting Salivary Secretion.

Background: Although low-level laser therapy (LLLT) is a widely used noninvasive treatment because of photobiomodulation effects, its application for xerostomia remained uncertain. Tight junctions (TJs), mainly composed of claudins, occludin, and ZO family members, are crucial structures that determine material transport through paracellular pathway in salivary gland epithelial cells. This work aimed to investigate whether LLLT affected salivary secretion through epithelial TJs. Methods: Transepithelial electrical resistance (TER) measurement and paracellular permeability assay were applied to evaluate paracellular permeability in submandibular gland (SMG)-C6 cells after irradiation with 540 nm green light. Immunofluorescence and western blot were used to detect the expression of TJ proteins. Quantitative phosphoproteomics were performed to explore possible intracellular signals. Results: We found that irradiation with 540 nm green light significantly decreased TER values while increased paracellular transport in SMG-C6 cells. 540 nm green light-induced redistribution of claudin-1, -3, and -4, but not occludin or ZO-1. Moreover, above phenomena were abolished by preincubation with capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. Notably, irradiation with 540 nm green light on the skin covering the whole submandibular gland regions promoted salivary secretion and attenuated lymphocytic infiltration in 21-week-old non-obese diabetic mice (n = 5 per group), a xerostomia animal model for Sjögren's syndrome. Through in-depth bioinformatics analysis and expression verification, ERK1/2 and EphA2 served as potential canonical and noncanonical signals underlying 540 nm green light. Conclusions: Our findings uncovered the novel therapeutic effects of 540 nm green light on xerostomia through regulation on the expression and distribution of TJs.

The prognostic value of pretreatment 18F-FDG PET-CT parameters with peripheral blood markers in patients with de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To develop and validate a prognostic nomogram based on pretreatment 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT)radiomics parameters and peripheral blood markers for risk stratification in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC). MATERIALS AND METHODS: A total of 558 patients with dmNPC were retrospectively enrolled between 2011 and 2019. Eligible patients were randomly divided into training and validation cohorts (7:3 ratio). A Cox regression model was used to identify prognostic factors for overall survival (OS). The predictive accuracy and discriminative ability of the prognostic nomogram were determined using the concordance index (C-index) and calibration curve. RESULTS: Independent factors derived from multivariable analysis of the training cohort to predict death were lactate dehydrogenase levels, pretreatment Epstein-Barr virus DNA, total lesion glycolysis of locoregional lesions, number of metastatic lesions, and age, all of which were assembled into a nomogram with (nomogram B) or without PET-CT parameters (nomogram A). The C-index of nomogram B for predicting death was 0.70, which was significantly higher than the C-index values for nomogram A. Patients were then stratified into low- and high-risk groups based on the scores calculated using nomogram B for OS. The median OS was significantly higher in the low-risk group than in the high-risk group (69.60 months [95 % CI: 58.50-108.66] vs. 21.40 months [95 % CI: 19.20-23.90]; p＜0.01). All the results were confirmed in the validation cohort. CONCLUSION: The proposed nomogram including PET-CT parameters yielded accurate prognostic predictions for patients with dmNPC, enabling effective risk stratification for these patients.

Mxene-bpV plays a neuroprotective role in cerebral ischemia-reperfusion injury by activating the Akt and promoting the M2 microglial polarization signaling pathways.

Studies have shown that the inhibition of phosphatase and tensin homolog deleted on chromosome 10 (PTEN)was neuroprotective against ischemia/reperfusion(I/R) injury. Bisperoxovanadium (bpV), a derivative of vanadate, is a well-established inhibitor of PTEN. However, its function islimited due to its general inadequacy in penetrating cell membranes. Mxene(Ti3C2Tx) is a novel two-dimensional lamellar nanomaterial with an excellent ability to penetrate the cell membrane. Yet, the effects of this nanomaterial on nervous system diseases have yet to be scrutinized. Here, Mxene(Ti3C2Tx) was used for the first time to carry bpV(HOpic), creating a new nanocomposite Mxene-bpV that was probed in a cerebral I/R injury model. The findings showed that this synthetic Mxene-bpV was adequately stable and can cross the cell membraneeasily. We observed that Mxene-bpV treatment significantly increased the survival rate of oxygen glucose deprivation/reperfusion(OGD/R)--insulted neurons, reduced infarct sizes and promoted the recovery of brain function after mice cerebral I/R injury. Crucially, Mxene-bpV treatment was more therapeutically efficient than bpV(HOpic) treatment alone over the same period. Mechanistically, Mxene-bpV inhibited the enzyme activity of PTEN in vitro and in vivo. It also promoted the expression of phospho-Akt (Ser473) by repressing PTEN and then activated the Akt pathway to boost cell survival. Additionally, in PTEN transgenic mice, Mxene-bpV suppressed I/R-induced inflammatory response by promoting M2 microglial polarization through PTEN inhibition. Collectively, the nanosynthetic Mxene-bpV inhibited PTEN' enzymatic activity by activating Akt pathway and promoting M2 microglial polarization, and finally exerted neuroprotection against cerebral I/R injury.

Case report: The diagnostic pitfall of Warthin-like mucoepidermoid carcinoma.

Warthin-like mucoepidermoid carcinoma (WL-MEC) is a newly reported variant of mucoepidermoid carcinoma. Its histological feature is easy to confused with metaplastic Warthin Tumor, and its relationship with Warthin tumor in histogenesis is controversial. In this study, we presented two cases of WL-MEC, discussing their clinicopathological and molecular features. Notably, one case was initially misdiagnosed during the first onset of the tumor. Case 1 was a 60-year-old female with a mass in the right parotid gland. Case 2 featured a 29-year-old male who developed a lump at the original surgical site 6 months after a "Warthin tumor" resection from the submandibular gland. Histologically, both tumor exhibited a prominent lymphoid stroma and cystic pattern, accompanied by various amounts of epithelial nests composed of squamoid cells, intermediate cells and mucinous cells. The characteristic eosinophilic bilayer epithelium of Warthin tumor was not typically presented in either case. Both cases tested positive for MAML2 gene rearrangement. To contextualize our findings, we conducted a comprehensive review of forty-eight WL-MEC cases documented in the English literature, aiming to synthesizing a reliable differential diagnostic approach. WL-MEC is a rare yet clinically relevant variant, posing a diagnostic pitfall for pathologists. Our study underscores the importance of a meticulous evaluation of both clinical and histological features, coupled with the detection of MAML2 rearrangement, as a credible method for distinguishing WL-MEC from other benign and malignant lesions, particularly metaplastic Warthin tumor.

Primary pulmonary myxoid sarcoma in the interlobar fissure of the left lung lobe: a case report.

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis. CASE DEMONSTRATION: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period. CONCLUSIONS: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.

Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.

Gastric cancer is one of the most common cancers and is considered the 5th most frequent occurring cancer worldwide. It has gained great attention from the clinicians and researchers because of high mortality rate. It is generally treated with chemotherapy, radiotherapy, and surgery. Recently, additional treatment options including immunotherapy and targeted therapy and immunotherapy have been developed. However, poor prognosis, limited survival rate of patients, and drug resistance to treatment remain critical problems. To improve treatment options or to overcome the bottleneck of treatment, identification of diagnostic and prognostic markers, determining the most effective therapeutic options, and uncovering the molecular regulations associated with treatment strategies are required. In this regard n6-methyladenosine (m6A) regulation is considered important. This reversible modification plays a crucial role in progression, development and treatment of HER2-positive gastric cancer. Here, we discuss the role of m6A modification in HER2-positive gastric cancer progression through collecting related studies at present. We further discuss the association of m6A modification with therapeutic efficacy in HER2-positive gastric cancer and list some examples. We conclude that modification of m6A can be a new strategy for improving the prognosis and survival rate of HER2-positive gastric cancer patients.

Sarcopenia and survival in colorectal cancer without distant metastasis: a systematic review and meta-analysis.

BACKGROUND AND AIM: Despite prior attempts to evaluate the effects of sarcopenia on survival among patients with colorectal cancer (CRC), the results of these studies have not been consistent. The present study aimed to evaluate the association between sarcopenia and survival among patients having CRC without distant metastasis by aggregating multiple studies. METHODS: We performed a literature search using computerized databases and identified additional studies from among the bibliographies of retrieved articles. The quality of each study was evaluated using the Newcastle-Ottawa Scale, and meta-analyses were performed to evaluate overall survival (OS) and disease-free survival (DFS). RESULTS: Thirteen studies with up to 6600 participants were included in the meta-analyses, with a mean age of 63.6 years (range: 18-93 years). We found that preoperative sarcopenia was associated with worse OS (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.38-1.88) and worse DFS (HR: 1.57; 95% CI: 1.10-2.24). Compared with patients without sarcopenia after tumor resection, those with postoperative sarcopenia had worse OS (HR: 1.76; 95% CI: 1.47-2.10) and DFS (HR: 1.79; 95% CI: 1.46-2.20). CONCLUSION: These meta-analyses suggest that sarcopenia, no matter observed before or after tumor resection, is associated with worse OS and DFS in patients with CRC who have no distant metastasis.

Interleukin-1 receptor 1 deficiency worsens hepatocellular carcinoma, while gemcitabine treatment alleviates the hepatocellular carcinoma-induced increase in intra-hepatic immune cells.

BACKGROUND AND AIM: Primary liver cancer, particularly hepatocellular carcinoma (HCC), represents a substantial global health challenge. Although immune checkpoint inhibitors are effective in HCC treatment, several patients still experience disease progression. Interleukin-1 (IL-1) regulates immunity and inflammation. We investigate the role of IL-1 in HCC development and progression and determine the potential therapeutic impact of gemcitabine in treating HCC. METHODS: Hydrodynamics-based transfection, employing the sleeping beauty transposase system, delivered surrogate tumor antigens, NRAS (NRAS proto-oncogene, GTPase), ShP53, and SB100 to C57BL/6 mice. A basic HCC mouse model was established. Pathogen-free animals were tested for serum and hepatotoxicity. The HCC prognosis was monitored using alanine aminotransferase and aspartate aminotransferase levels. Liver histology immunohistochemistry and mouse splenocyte/intra-hepatic immune cell flow cytometry were conducted. IL-1ß levels in human and mouse serum were assessed. RESULTS: Interleukin-1ß levels were elevated in patients with HCC compared with those in non-HCC controls. Hepatic IL-1ß levels were higher in HCC mouse models than those in non-HCC mice, suggesting localized hepatic inflammation. IL-1 receptor type 1 (IL-1R1) knockout (IL-1R1-/-) mice exhibited less severe HCC progression than that in wild-type mice, despite the high intra-hepatic IL-1ß concentration. IL-1R1-/- mice exhibited increased hepatic levels of myeloid-derived suppressor cells and regulatory T cells, which may exacerbate HCC. Gemcitabine significantly reduced the HCC tumor burden, improved liver conditions, and increased survival rates in HCC mouse models. Gemcitabine reduced the hepatic levels of myeloid-derived suppressor cells and regulatory T cells, potentially alleviating immune suppression in the liver. CONCLUSIONS: Targeting IL-1 or combining gemcitabine with immunotherapy is a promising approach for treating advanced-stage HCC.

Measurable residual disease testing by next generation sequencing is more accurate compared with multiparameter flow cytometry in adults with B-cell acute lymphoblastic leukemia.

Results of measurable residual disease (MRD)-testing by next-generation sequencing (NGS) correlate with relapse risk in adults with B-cell acute lymphoblastic leukemia (ALL) receiving chemotherapy or an allotransplant from a human leukocyte antigen (HLA)-identical relative or HLA-matched unrelated donor. We studied cumulative incidence of relapse (CIR) and survival prediction accuracy using a NGS-based MRD-assay targeting immunoglobulin genes after 2 courses of consolidation chemotherapy cycles in 93 adults with B-cell ALL most receiving HLA-haplotype-matched related transplants. Prediction accuracy was compared with MRD-testing using multi-parameter flow cytometry (MPFC). NGS-based MRD-testing detected residual leukemia in 28 of 65 subjects with a negative MPFC-based MRD-test. In Cox regression multi-variable analyses subjects with a positive NGS-based MRD-test had a higher 3-year CIR (Hazard Ratio [HR] = 3.37; 95 % Confidence Interval [CI], 1.34-8.5; P = 0.01) and worse survival (HR = 4.87 [1.53-15.53]; P = 0.007). Some data suggest a lower CIR and better survival in NGS-MRD-test-positive transplant recipients but allocation to transplant was not random. Our data indicate MRD-testing by NGS is more accurate compared with testing by MPFC in adults with B-cell ALL in predicting CIR and survival. (Registered in the Beijing Municipal Health Bureau Registration N 2007-1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTROPC-14005546]).

Application of 3-dimensional visualization and image fusion technology in liver cancer with portal vein tumor thrombus surgery.

Liver cancer with portal vein tumor thrombus (PVTT) is a frequent finding and is related to poor prognosis. Surgical resection provides a more promising prognosis in selected patients. The purpose of this study was to explore the application of 3D (3-dimensional) visualization and image fusion technology in liver cancer with PVTT surgery. 12 patients were treated with surgery between March 2019 and August 2022. The preoperative standard liver volume (SLV), estimated future liver remnant (FLR), FLR/SLV, 3D visualization models, PVTT classification, operation programs, surgical results, and prognosis were collected and analyzed. Twelve patients who had complete data of 3D visualization and underwent hemihepatectomy combined with portal vein tumor thrombectomy. The operation plan was formulated by 3D visualization and was highly consistent with the actual surgery. The SLV was 1208.33 ±â€…63.22 mL, FLR was 734.00 mL and FLR/SLV was 61.62 ±â€…19.38%. The accuracy of classification of PVTT by 3D visualization was 100%, Cheng type Ⅱa (4 cases), Ⅱb (2 cases), Ⅲa (4 cases), and Ⅲb (2 cases). The 3D visualization model was a perfect fusion with the intraoperative live scene and precise guidance for hepatectomy. No patient was suffering from postoperative liver failure and without procedure­associated death. 6 patients died of tumor recurrence, and 2 patients died of other reasons. The 12-month cumulative survival rate was 25.9%. 3D visualization and image fusion technology could be used for precise assessment of FLR, classification of PVTT, surgery navigation, and which was helpful in improving the safety of hepatectomy.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

Clinical Diagnostic Value of circ-ARHGER28 for Breast Cancer and its Effect on MCF 7 Cell Proliferation and Apoptosis.

BACKGROUND/AIM: Clinical diagnostic value of circ-ARHGER28 in breast cancer (BC), and the biological functions of circ-ARHGER28 on the proliferation and apoptosis of MCF-7 cells were investigated. MATERIALS AND METHODS: Human circRNA microarray was performed to analyze the expression of circRNAs in BC patients. RT-qPCR combined with bioinformatics analysis was applied to verify the candidate circRNAs in BC tissues and peripheral blood samples. Circ-ARHGER28 was chosen as the candidate gene for further research. The clinical diagnostic value and biological functions of circ-ARHGER28 were analyzed. The overexpression and negative control vector of circ-ARHGER28 were constructed and transfected to MCF-7 cells. The CCK 8 assay and clone formation experiments were applied to detect the cell proliferative and migratory abilities. Flow cytometry was used to analyze cell apoptosis and cell cycle distribution. RT-qPCR and Western blot were performed to detect apoptosis and expression of PI3K/AKT/mTOR-associated genes and proteins. RESULTS: Overexpression of circ-ARHGER28 inhibited the proliferation, colony formation and migration of MCF-7 cells, while increasing the population of the cells in the G2/M phase and the apoptotic rate. Apoptosis associated genes and proteins were significantly increased, whereas gene and protein expression of PI3K, AKT and mTOR were decreased in the cells. CONCLUSION: Circular RNA ARHGER28 exhibits promising diagnostic value for BC. Circ-ARHGER28 inhibited MCF-7 cell proliferation and increased the apoptotic rate. The function of circ-ARHGER28 was associated with the PI3K/AKT/mTOR signaling pathway. Circ-ARHGER28 could be an ideal biomarker for BC diagnosis and a novel target for BC therapy.

Synthesis of All-Benzene Multi-Macrocyclic Nanocarbons by Post-Functionalization of meta-Cycloparaphenylenes.

Expanding the diversity of multi-macrocyclic nanocarbons, particularly those with all-benzene scaffolds, represents intriguing yet challenging synthetic tasks. Complementary to the existing synthetic approaches, here we report an efficient and modular post-functionalization strategy that employs iridium-catalyzed C-H borylation of the highly strained meta-cycloparaphenylenes (mCPPs) and an mCPP-derived catenane. Based on the functionalized macrocyclic synthons, a number of novel all-benzene topological structures including linear and cyclic chains, polycatenane, and pretzelane have been successfully prepared and characterized, thereby showcasing the synthetic utility and potential of the post-functionalization strategy.

New steroids from mangrove-associated fungus Trichoderma asperellum SCNU-F0048.

Chemical investigation of the fungus Trichoderma asperellum SCNU-F0048 led to the discovery of two new steroids, ergosta-4,6,8 (14),22-tetraen-3-(3'-methyl-4'-hydroxyl-γ-butenolide) (1) and camphosterol B (2), as well as two known compounds, i.e. stigmasta-4,6,8(14),22-tetraen-3-one (3) and 4-hydroxy-17- methylincisterol (4). Their structures were elucidated by extensive nuclear mangnetic resonance, spectrum analysis and single crystal X-ray diffraction analysis. Bioassay disclosed that compound 1 showed strong cytotoxicity to a panel of tumor cell lines. Moreover, compounds 1 and 2 showed excellent antifungal activity against Penicillium italicum with IC50 values of 0.016 and 0.022 µM, respectively.

Circ_0012152 Accelerates Acute Myeloid Leukemia Progression through the miR-652-3p/SOX4 Axis.

OBJECTIVE: Acute myeloid leukemia (AML) is an aggressive hematological malignancy characterized by abnormal myeloid blast expansion. Recent studies have demonstrated that circular RNAs play a role in AML pathogenesis. In this study, we aimed to investigate the clinical significance of circ_0012152 in AML and elucidate its underlying molecular mechanism in the pathogenesis of this condition. METHODS: Circ_0012152 expression was detected by quantitative real-time polymerase chain reaction in samples obtained from 247 patients with AML and 40 healthy controls. A systematic analysis of clinical characteristics and prognostic factors was also conducted. Cell growth was assessed using the Cell Counting Kit-8 (CCK-8) assay, and apoptosis and cell cycle progression were evaluated by flow cytometry. Moreover, RNA pull-down was performed to identify target microRNAs, and transcriptome RNA sequencing and bioinformatics analyses were utilized to identify downstream mRNA targets. RESULTS: Circ_0012152 was significantly upregulated in samples from patients with AML and served as an independent adverse prognostic factor for overall survival (OS) (hazard ratio: 2.357; 95% confidence interval 1.258-4.415). The circ_0012152 knockdown reduced cell growth, increased apoptosis, and inhibited cell cycle progression in AML cell lines. RNA pull-down and sequencing identified miR-652-3p as a target microRNA of circ_0012152. Cell growth inhibition by circ_0012152 knockdown was significantly relieved by miR-652-3p inhibitors. We suggested that miR-652-3p targeted SOX4, as the decrease in SOX4 expression resulting from circ_0012152 knockdown was upregulated by miR-652-3p inhibitors in AML cells. CONCLUSION: Circ_0012152 is an independent poor prognostic factor for OS in AML, and it promotes AML cell growth by upregulating SOX4 through miR-652-3p.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; 22(4): 494-503.

Experiences and preferences of truth-telling in families of children with cancer: A phenomenological study.

Objective: The delivery of bad news is an unpleasant but necessary medical procedure. However, few studies have addressed the experiences and preferences of the families of school-aged children with cancer when they are informed of the children's condition. This study aimed to explore families of school-age children with cancer for their preferences and experiences of truth-telling. Methods: This descriptive phenomenological qualitative research was conducted using focus group interviews and semistructured interview guidelines were adopted for in-depth interviews. Fifteen families participated in the study. The data were analyzed using Colaizzi's analysis. Data were collected from August 2019 to May 2020. Results: The study identified two major themes: "caught in a dilemma" and "kind and comprehensive team support." The first major theme focused on families' experiences with cancer truth-telling. Three sub-themes emerged: (1) cultural aspects of cancer disclosure, (2) decision-making regarding informing pediatric patients about their illness, and (3) content of disclosure after weighing the pros and cons. The second major theme, which revealed families' preferences for delivering bad news, was classified into three sub-themes: (1) have integrity, (2) be realistic, and (3) be supportive. Conclusions: This study underscores the dilemma encountered by the families of children with cancer after disclosure and their inclination toward receiving comprehensive information and continuous support. Health care personnel must improve their truth-telling ability in order to better address the needs of such families and to provide continuous support throughout the truth-telling process.