Ultrasound-based nomogram to predict the recurrence in papillary thyroid carcinoma using machine learning.

BACKGROUND AND AIMS: The recurrence of papillary thyroid carcinoma (PTC) is not unusual and associated with risk of death. This study is aimed to construct a nomogram that combines clinicopathological characteristics and ultrasound radiomics signatures to predict the recurrence in PTC. METHODS: A total of 554 patients with PTC who underwent ultrasound imaging before total thyroidectomy were included. Among them, 79 experienced at least one recurrence. Then 388 were divided into the training cohort and 166 into the validation cohort. The radiomics features were extracted from the region of interest (ROI) we manually drew on the tumor image. The feature selection was conducted using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. And multivariate Cox regression analysis was used to build the combined nomogram using radiomics signatures and significant clinicopathological characteristics. The efficiency of the nomogram was evaluated by receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to analyze the recurrence-free survival (RFS) in different radiomics scores (Rad-scores) and risk scores. RESULTS: The combined nomogram demonstrated the best performance and achieved an area under the curve (AUC) of 0.851 (95% CI: 0.788 to 0.913) in comparison to that of the radiomics signature and the clinical model in the training cohort at 3 years. In the validation cohort, the combined nomogram (AUC = 0.885, 95% CI: 0.805 to 0.930) also performed better. The calibration curves and DCA verified the clinical usefulness of combined nomogram. And the Kaplan-Meier analysis showed that in the training cohort, the cumulative RFS in patients with higher Rad-score was significantly lower than that in patients with lower Rad-score (92.0% vs. 71.9%, log rank P < 0.001), and the cumulative RFS in patients with higher risk score was significantly lower than that in patients with lower risk score (97.5% vs. 73.5%, log rank P < 0.001). In the validation cohort, patients with a higher Rad-score and a higher risk score also had a significantly lower RFS. CONCLUSION: We proposed a nomogram combining clinicopathological variables and ultrasound radiomics signatures with excellent performance for recurrence prediction in PTC patients.

Nomogram for predicting lymph node metastasis in patients with ovarian cancer using ultrasonography: a multicenter retrospective study.

BACKGROUND: Ovarian cancer is a common cancer among women globally, and the assessment of lymph node metastasis plays a crucial role in the treatment of this malignancy. The primary objective of our study was to identify the risk factors associated with lymph node metastasis in patients with ovarian cancer and develop a predictive model to aid in the selection of the appropriate surgical procedure and treatment strategy. METHODS: We conducted a retrospective analysis of data from patients with ovarian cancer across three different medical centers between April 2014 and August 2022. Logistic regression analysis was employed to establish a prediction model for lymph node metastasis in patients with ovarian cancer. We evaluated the performance of the model using receiver operating characteristic (ROC) curves, calibration plots, and decision analysis curves. RESULTS: Our analysis revealed that among the 368 patients in the training set, 101 patients (27.4%) had undergone lymph node metastasis. Maximum tumor diameter, multifocal tumor, and Ki67 level were identified as independent risk factors for lymph node metastasis. The area under the curve (AUC) of the ROC curve in the training set was 0.837 (95% confidence interval [CI]: 0.792-0.881); in the validation set this value was 0.814 (95% CI: 0.744-0.884). Calibration plots and decision analysis curves revealed good calibration and clinical application value. CONCLUSIONS: We successfully developed a model for predicting lymph node metastasis in patients with ovarian cancer, based on ultrasound examination results and clinical data. Our model accurately identified patients at high risk of lymph node metastasis and may guide the selection of appropriate treatment strategies. This model has the potential to significantly enhance the precision and efficacy of clinical management in patients with ovarian cancer.

Recent Advances in Imaging Agents Anchored with pH (Low) Insertion Peptides for Cancer Theranostics.

The acidic extracellular microenvironment has become an effective target for diagnosing and treating tumors. A pH (low) insertion peptide (pHLIP) is a kind of peptide that can spontaneously fold into a transmembrane helix in an acidic microenvironment, and then insert into and cross the cell membrane for material transfer. The characteristics of the acidic tumor microenvironment provide a new method for pH-targeted molecular imaging and tumor-targeted therapy. As research has increased, the role of pHLIP as an imaging agent carrier in the field of tumor theranostics has become increasingly prominent. In this paper, we describe the current applications of pHLIP-anchored imaging agents for tumor diagnosis and treatment in terms of different molecular imaging methods, including magnetic resonance T1 imaging, magnetic resonance T2 imaging, SPECT/PET, fluorescence imaging, and photoacoustic imaging. Additionally, we discuss relevant challenges and future development prospects.

Gas-Mediated Intestinal Microbiome Regulation Prompts the Methanol Extract of Schizonepetae Spica to Relieve Colitis.

Intestinal dysbiosis plays an important role in the pathogenesis of colitis (UC). Schizonepetae Herba can achieve anti-inflammatory effects as a medicine and food homologous vegetable. Luteolin, eriodictyol, fisetin, and kaempferol are the main anti-inflammatory active compounds obtained through mass spectrometry from the methanol extract of Schizonepetae Spica (JJSM). JJSM intervention resulted in attenuated weight loss, high disease-activity-index score, colon length shortening and colonic pathological damage in DSS-induced colitis mice. Interestingly, hydrogen sulfide (H2S) was inhibited remarkably, which is helpful to elucidate the relationship between active substance and intestinal flora. Furthermore, JJSM administration improved intestinal flora with down-regulating the abundance of harmful bacteria such as Clostridiales and Desulfovibrio and up-regulating the abundance of beneficial bacteria such as Muribaculaceae and Ligolactobacillus and enhanced the production of SCFAs. It is worth noticing that Desulfovibrio is related to the production of intestinal gas H2S. The elevated levels of Desulfovibrio and H2S will hasten the onset of colitis, which is a crucial risk factor for colitis. The results displayed that JJSM could considerably ameliorate colitis by rebuilding H2S-related intestinal flora, which provides a new therapeutic strategy for Schizonepetae Spica to be utilized as a functional food and considered as an emerging candidate for intestinal inflammation.

The Role of Intestinal Flora in Anti-Tumor Antibiotic Therapy.

Anti-tumor antibiotics are chemical substances produced by micro-organisms to control cancer development. Some of the currently used cancer treatment regimens are anti-tumor antibiotics. However, many studies have demonstrated that anti-tumor antibiotics may have adverse effects on normal cells. This calls for development of strategies to alleviate these negative effects and improve cancer treatment. Recent studies have suggested that the efficacy of anti-tumor antibiotics may be affected by intestinal microbiota. For instance, intestinal microbiota can alleviate the negative effects of antibiotic treatment and regulate the tumor immune micro-environment. In this way, anti-tumor antibiotics can improve tumor control. However, the specific mechanisms need to be further explored. This review discusses the effect of intestinal flora on anti-tumor antibiotic therapy and summarizes the specific mechanisms by which antibiotics inhibit harmful intestinal micro-organisms and promote efficacy of probiotics, which may improve the control of neoplasm development and growth.

Dual Role of Indoles Derived From Intestinal Microbiota on Human Health.

Endogenous indole and its derivatives (indoles), considered as promising N-substituted heterocyclic compounds, are tryptophan metabolites derived from intestinal microbiota and exhibit a range of biological activities. Recent studies indicate that indoles contribute to maintaining the biological barrier of the human intestine, which exert the anti-inflammatory activities mainly through activating AhR and PXR receptors to affect the immune system's function, significantly improving intestinal health (inflammatory bowel disease, hemorrhagic colitis, colorectal cancer) and further promote human health (diabetes mellitus, central system inflammation, and vascular regulation). However, the revealed toxic influences cannot be ignored. Indoxyl sulfate, an indole derivative, performs nephrotoxicity and cardiovascular toxicity. We addressed the interaction between indoles and intestinal microbiota and the indoles' effects on human health as double-edged swords. This review provides scientific bases for the correlation of indoles with diseases moreover highlights several directions for subsequent indoles-related studies.

The Methanol Extract of Polygonatum odoratum Ameliorates Colitis by Improving Intestinal Short-Chain Fatty Acids and Gas Production to Regulate Microbiota Dysbiosis in Mice.

The potential impacts of methanol extract from Polygonatum odoratum on (YZM) colonic histopathology, gut gas production, short-chain fatty acids (SCFAs), and intestinal microbiota composition were evaluated with dextran sulfate sodium (DSS)-induced colitis mice in this study. These results indicated that YZM increased colon length and ameliorated colonic histopathology in DSS-induced colitis mice. Moreover, YZM administration reversed intestinal microbiota compositions leading to the inhibition of H2S-related bacteria (e.g., Desulfovibrionaceae) and the lower level of H2S and higher contents of SCFA-related bacteria (e.g., Muribaculaceae). Taken together, the effects of methanol extract from Polygonatum odoratum are studied to provide new enlightenment and clues for its application as a functional food and clinical drug. Our study first revealed the relationship between intestinal gas production and key bacteria in ulcerative colitis.

Methanol extract of Inonotus obliquus improves type 2 diabetes mellitus through modifying intestinal flora.

Type 2 diabetes mellitus (T2DM) poses a significant risk to human health. Previous research demonstrated that Inonotus obliquus possesses good hypolipidemic, anti-inflammatory, and anti-tumor properties. In this research, we aim to investigate the potential treatment outcomes of Inonotus obliquus for T2DM and discuss its favourable influences on the intestinal flora. The chemical composition of Inonotus obliquus methanol extracts (IO) was analyzed by ultra-high-performance liquid chromatography-Q extractive-mass spectrometry. IO significantly improved the blood glucose level, blood lipid level, and inflammatory factor level in T2DM mice, and effectively alleviated the morphological changes of colon, liver and renal. Acetic acid, propionic acid, and butyric acid levels in the feces of the IO group were restored. 16S rRNA gene sequencing revealed that the intestinal flora composition of mice in the IO group was significantly modulated. Inonotus obliquus showed significant hypoglycemic and hypolipidemic effects with evident anti-inflammatory activity and improved the morphological structure of various organs and cells. Inonotus obliquus increased the levels of short-chain fatty acids in the environment by increasing the population of certain bacteria that produce acid, such as Alistipes and Akkermansia, which are beneficial to improve intestinal flora disorders and maintain intestinal flora homeostasis. Meanwhile, Inonotus obliquus further alleviated T2DM symptoms in db/db mice by down-regulating the high number of microorganisms that are dangerous, such as Proteobacteria and Rikenellaceae_RC9_gut_group and up-regulating the abundance of beneficial bacteria such as Odoribacter and Rikenella. Therefore, this study provides a new perspective for the treatment of T2DM by demonstrating that drug and food homologous active substances could relieve inflammation via regulating intestinal flora.

TRPC1 Deficiency Impairs the Endothelial Progenitor Cell Function via Inhibition of Calmodulin/eNOS Pathway.

Endothelial progenitor cells (EPCs) promote angiogenesis and play a pivotal role in endothelial repair and re-endothelialization after vascular injury. Transient receptor potential-canonical1 (TRPC1) has been recently implied to play important roles on EPC function. Here, we studied the role of TRPC1 in regulating EPC function in vivo and in vitro. EPCs were cultured from TRPC1-knockout mice and their controls. In vitro, TRPC1 knockout reduced EPC functional activities, including migration and tube formation. Additionally, calmodulin (CaM)/endothelial nitric oxide synthase (eNOS) signaling activity were downregulated after TRPC1 knockout. Administration of CaM or eNOS inhibitor ameliorated TRPC1 knockout-reduced EPC migration and tube formation. In vivo Matrigel plug assay confirmed that TRPC1 knockout decreased formation of functional blood vessels of EPCs compared with wild-type EPCs. Taken together, these data suggest that TRPC1 is a critical regulator of angiogenesis.

Anti-colorectal cancer effects of tripolinolate A from Tripolium vulgare.

Tripolinolate A (TLA) is recently identified as a new compound from a halophyte plant Tripolium vulgare and has been shown to have significant in vitro activity against the proliferation of colorectal cancer and glioma cells. This study was designed to further investigate the effects of TLA on the proliferation of human normal cells, and the apoptosis and cell cycle in colorectal cancer cells, and the growth of tumors in the colorectal cancer-bearing animals. The data obtained from this study demonstrated that: 1) TLA had much less cytotoxicity in the human normal cells than the colorectal cancer cells; 2) TLA remarkably induced apoptosis in the human colorectal cancer cells and blocked cell cycle at G2/M phase, and 3) TLA had significant anti-colorectal cancer activity in the tumor-bearing animals.

Antiproliferative cyclodepsipeptides from the marine actinomycete Streptomyces sp. P11-23B downregulating the tumor metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis.

Two cyclodepsipeptides and a known cyclodepsipeptide valinomycin were isolated from a culture of the marine actinomycete Streptomyces sp. P11-23B. Their structures were established based on NMR, HRESIMS, and MS-MS spectroscopic interpretation as well as by chemical degradation. Both streptodepsipeptides P11A and P11B inhibited proliferation of different glioma cell lines, with IC50 values ranging from 0.1 µM to 1.4 µM. Streptodepsipeptide P11A was found to block the cell cycle at the G0/G1 phase and induce apoptosis in glioma cells. Further investigation demonstrated that streptodepsipeptide P11A downregulated expression of HK2, PFKFB3, PKM2, GLS, and FASN, important tumor metabolic enzymes. Data from this study suggested that targeting multiple tumor metabolic regulators might be one anti-glioma mechanism of streptodepsipeptide P11A. A possible mechanism for this class of streptodepsipeptides is reported herein.

New streptophenazines from marine Streptomyces sp. 182SMLY.

Six phenazines including three new ones were isolated from the culture of a marine actinomycete Streptomyces sp. 182SMLY. Based on the analyses of NMR, HRESIMS, optical rotation value, and CD data, the structures of these isolated compounds were determined as new phenazines of (-)-streptophenazines M-O and known phenazines of 1-carbomethoxyphenazine and (-)-streptophenazines A and B. (-)-Streptophenazine B showed activity in suppressing the growth of methicillin-resistant Staphylococcus aureus with MIC value of 4.2 µg/mL.

Novel propanamide analogue and antiproliferative diketopiperazines from mangrove Streptomyces sp. Q24.

A new propanamide analogue (1), along with one known alkaloid (2) and four known diketopiperazines (3-6), was isolated from a cultured broth of the actinomycete Streptomyces sp. Q24 that was obtained from a sample of mangrove soil. The structures of these isolates were characterised as 3-acetylamino-N-2-thienyl-propanamide (1), N-acetyltryptamine (2), cyclo-(l-phenylalanine-l-4-hydroxyproline) (3), cyclo-(l-leucine-l-4-hydroxyproline) (4), cyclo-(l-phenylalanine-d-4-hydroxyproline) (5) and cyclo-(l-leucine-l-proline) (6) based on their NMR and HRESIMS data as well as optical rotation. Three diketopiperazines (3, 4, 6) showed activity in inhibiting the proliferation of human glioma U87-MG and U251 cells. This type of the new propanamide analogue (1) is first found from a nature source and the antiproliferative property of these three diketopiperazines against glioma cells is also reported herein for the first time.

New Metabolites and Bioactive Actinomycins from Marine-Derived Streptomyces sp. ZZ338.

An extract prepared from the culture of a marine-derived actinomycete Streptomyces sp. ZZ338 was found to have significant antimicrobial and antiproliferative activities. A chemical investigation of this active extract resulted in the isolation of three known bioactive actinomycins (1-3) and two new metabolites (4 and 5). The structures of the isolated compounds were identified as actinomycins D (1), V (2), X0ß (3), 2-acetylamino-3-hydroxyl-4-methyl-benzoic acid methyl ester (4), and N-1S-(4-methylaminophenylmethyl)-2-oxo-propyl acetamide (5) based on their nuclear magnetic resonance (NMR) and high resolution electrospray ionization mass spectroscopy (HRESIMS) data as well as their optical rotation. This class of new compound 5 had never before been found from a natural resource. Three known actinomycins showed activities in inhibiting the proliferation of glioma cells and the growth of methicillin-resistant Staphylococcus aureus, Escherichia coli, and Candida albicans and are responsible for the activity of the crude extract. Actinomycin D (1) was also found to downregulate several glioma metabolic enzymes of glycolysis, glutaminolysis, and lipogenesis, suggesting that targeting multiple tumor metabolic regulators might be a new anti-glioma mechanism of actinomycin D. This is the first report of such a possible mechanism for the class of actinomycins.

Bioactive Polycyclic Quinones from Marine Streptomyces sp. 182SMLY.

Chemical investigation of the cultures of marine Streptomyces sp. 182SMLY led to the discovery of two new polycyclic anthraquinones, which were elucidated as N-acetyl-N-demethylmayamycin (1) and streptoanthraquinone A (2) based on the extensive spectroscopic analysis including 2D NMR, HRESIMS, and an electronic circular dichroism (ECD) calculation. Both anthraquinones remarkably suppressed the proliferation of four different glioma cell lines with IC50 values in a range from 0.5 to 7.3 µM and induced apoptosis in the glioma cells. The ratios of IC50 for normal human astrocytes to IC50 for glioma cells were 6.4-53 for 1 and >14-31 for 2. N-acetyl-N-demethylmayamycin (1) also inhibited the growth of methicillin-resistant Staphylococcus aureus with MIC 20.0 µM.

A new curvularin glycoside and its cytotoxic and antibacterial analogues from marine actinomycete Pseudonocardia sp. HS7.

Five curvularin macrolides (1-5) were isolated from the cultured broth of marine actinomycete Pseudonocardia sp. HS7 that was obtained from the cloacal aperture of sea cucumber Holothuria moebii. The structures of these isolates were characterized as (11S,15R)-11-hydroxycurvularin (1), (11R,15R)-11-hydroxycurvularin (2), curvularin-7-O-α-D-glucopyranoside (3), trans-dehydrocurvularin (4) and curvularin (5) based on their NMR and HRESIMS data as well as chemical degradation. Compound 3 is a new macrolide with a rare α-D-glucopyranose substituent. Compounds 1-4, 5a and 5c (the acyl products of 5), suppressed the proliferation of all six tested cancer cell lines and 4 is the most active compound with IC50 values ranging from 0.59 to 3.39 µM. The 11-hydroxycurvularins 1 and 2 also showed antibacterial activity inhibiting the growth of Escherichia coli.

Cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii.

BACKGROUND: Whether sulfated saponins from Holothuria moebii inhibit the proliferation of colorectal cancer cells and have anti-colorectal tumor effects in animal model has not been investigated. PURPOSE: To evaluate the cytotoxic and anti-colorectal tumor effects of sulfated saponins from sea cucumber Holothuria moebii. METHOD: (1) Column chromatography was used to prepare the total and individual saponins and HPLC was applied to define the components of the total saponins; (2) the activity of the total and individual saponins inhibiting the proliferation of human colorectal cancer cells was determined by SRB assay and the apoptosis induced by the saponins was qualified using cytometric analysis with Annexin V-FITC/PI double staining; and (3) the antitumor effects of the sulfated saponins on colorectal CT-26 tumor-bearing Balb/c mice were tested. RESULTS: The total and individual sulfated saponins significantly inhibited the proliferation of four different human colorectal cancer cells with IC50 values ranging from 1.04 to 4.08 µM (or 1.46 to 3.24 µg/ml for total saponins) and induced late apoptosis at an early treatment time in cancer cells. The total saponins (120 mg/kg) had antitumor activity in colorectal CT-26 tumor-bearing Balb/c mice. CONCLUSION: The sulfated saponins from H. moebii remarkably inhibited the proliferation of different human colorectal cancer cells and had significant anti-colorectal tumor activity in animal model.

Bioactive sulfated saponins from sea cucumber Holothuria moebii.

The bioactive ingredients of sea cucumber Holothuria moebii were investigated, and four sulfated saponins (1-4) and one desulfated saponin (3B) with an unusual 3,4-epoxy xylose were obtained from this study. Compound 2 is a new triterpenoid saponin and 3B is a new artificial compound. On the basis of the extensive NMR and HRESIMS data, their structures were assigned as 3-O-[ß-D-quinovopyranosyl-(1 → 2)-4-sodium sulfato-ß-D-xylopyranosyl]-25-acetoxy-22-oxo-9(11)-holostene-3ß,12α,17α-triol (2) and 3-O-[ß-D-quinovopyranosyl-(1 → 2)-3,4-epoxy-ß-xylopyranosyl]-22,25-epoxy-9(11)-holostene-3ß,12α,17α-triol (3B). Compounds 1-4 showed activity suppressing the proliferation of four different glioma cells with IC50 values ranging from 0.99 to 8.64 µM. New saponin 2 significantly induced apoptosis in human glioblastoma U87-MG cells and reduced the expression levels of several glioma metabolic enzymes of glycolysis and glutaminolysis. This study reveals for the first time that selectively targeting multiple glioma metabolic regulators of glycolysis and glutaminolysis might be one of the anti-glioma mechanisms of saponin 2.

Bioactive triterpenoid saponins and phenolic compounds against glioma cells.

A total of 54 natural origin compounds were evaluated for their activity in inhibiting the proliferation of glioma cells. Results showed that four Aesculus polyhydroxylated triterpenoid saponins (3-6), six Gleditsia triterpenoid saponins (7-12), and five phenolic compounds (43-46, 51) had dose-dependent activity suppressing the proliferation of both C6 and U251 cells. Structure-activity relationship analysis suggested that the acetyl group at C-28 for the Aesculus saponins and the monoterpenic acid moiety for the Gleditsia saponins could be critical for the activity of these active compounds. Aesculioside H (4), gleditsioside A (7), and feuric acid 3,4-dihydroxyphenethyl ester (FADPE, 46) were the three most active compounds from the different types of the active compounds and induced apoptosis and necrosis in glioma cells.

Polyoxygenated 24,28-epoxyergosterols inhibiting the proliferation of glioma cells from sea anemone Anthopleura midori.

Eleven sterols (1-11) and one carotenoid (12) were isolated and identified from sea anemone Anthopleura midori. Compounds 1-6 are rare polyoxygenated ergosterols with a 24,28-epoxy moiety. The structures of these epoxyergosterols were determined by NMR and HRESIMS analyses as well as their chemical-physical properties. Epoxyergosterols 1 and 2 were found to be new natural products and 3-6 are new compounds. Bioactive assay showed that compounds 1, 2, 3, 5, 7, 8, 11, and 12 inhibited the proliferation of rat glioma C6 and human glioma U251 cells with IC50 in a range of 2.41-80.45 µM. Further investigation suggested that 1 and 3 induced apoptosis in glioma cells and 1 blocked U251 cells at the G0/G1 phase.