Phyllanthi Tannin Loaded Solid Lipid Nanoparticles for Lung Cancer Therapy: Preparation, Characterization, Pharmacodynamics and Safety Evaluation.

The objective of the present study was to develop PTF-loaded solid lipid nanoparticles (PTF-SLNs) and investigate their efficacy in treating lung cancer. The PTF-SLNs were prepared by the thin film hydration method and verified by FTIR and TEM. Their physicochemical properties were characterized by particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE), drug loading (DL), etc. Then, the pharmacodynamic studies of PTF-SLNs were performed on Lewis lung cancer cells and tumor-bearing mice. Finally, the safety studies were assessed by organ index, serum biochemical indicators, and histopathological changes. The PTF-SLNs were characterized by around 50 nm sphere nanoparticles, sustained ideal stability, and controlled drug release effects. The pharmacodynamic evaluation results showed that PTF-SLNs had stronger anti-tumor efficacy than PTF. An in vitro study revealed a more obvious cytotoxicity and apoptosis effect. The IC 50 values of PTF and PTF-SLNs were 67.43 µg/mL and 20.74 µg/mL, respectively. An in vivo study showed that the tumor inhibition rates of 2 g/kg PTF and 0.4 g/kg PTF-SLNs were 59.97% and 64.55%, respectively. The safety preliminary study indicated that PTF-SLNs improve the damage of PTF to normal organs to a certain extent. This study provides a nanoparticle delivery system with phenolic herbal extract to improve anti-tumor efficacy in lung cancer.

The Therapeutic Effect and the Potential Mechanism of Flavonoids and Phenolics of Moringa oleifera Lam. Leaves against Hyperuricemia Mice.

The aim of this study is to evaluate the anti-hyperuricemia effect and clarify the possible mechanisms of flavonoids and phenolics of MOL (MOL-FP) in mice. Hyperuricemia mice were generated via intraperitoneal (i.p.) administration of potassium oxonate (PO) and oral gavage (p.o.) of hypoxanthine (HX). Serum uric acid (UA), weight, serum XO activity, hepatic XO activity, urea nitrogen (BUN), creatinine (CRE), serum AST level, serum ALT level, mRNA expression of renal urate-anion transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), organic anion transporters 3 (OAT3), and ATP-binding cassette transporter G2 (ABCG2) were determined. The molecular docking was conducted using AutoDock Vina 1.2.0 to screen potential XO inhibitors in MOL-FP. Serum metabolomics was established to collect the metabolic profiles of mice and explore the metabolic changes that occurred after MOL-FP treatment. MOL-FP could notably reduce the serum UA level of hyperuricemia mice by inhibiting XO activity and regulating renal urate transporters. Molecular docking studies indicated that 5-p-coumaroylquinic acid, 3-p-coumaroylquinic acid, and catechin could be potential XO inhibitors. Besides, MOL-FP prevented the pathological process of hyperuricemia by regulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism.

Prenatal diagnosis of Meier-Gorlin syndrome 7: a case presentation.

BACKGROUND: Meier-Gorlin syndrome 7 (MGS7) is a rare autosomal recessive condition. We reported a fetus diagnosed with Meier-Gorlin syndrome 7. The antenatal sonographic images were presented, and compound heterozygous mutations of CDC45 on chromosome 22 were identified by whole-exome sequencing (WES). CASE PRESENTATION: Fetal growth restriction (FGR), craniosynostosis, and brachydactyly of right thumb were found in a fetus of 28th gestational weeks. The fetus was diagnosed as MGS7 clinically. After extensive counseling, the couple opted for prenatal diagnosis by cordocentesis and termination of pregnancy. Karyotype analysis and WES were performed. Chromosomal karyotyping showed that the fetus was 46, XY. There were 2 mutations of CDC45, the causal gene of MGS7 on chromosome 22, which were inherited from the couple respectively were identified by WES. Facial dysmorphism, brachydactyly of right thumb, and genitalia abnormally were proved by postpartum autopsy, and craniosynostosis was confirmed by three-dimensional computed tomography (3D-CT) reconstruction. CONCLUSIONS: It is possible to detect multiple clinical features of Meier-Gorlin syndrome in prenatal sonography. Deteriorative FGR complicated with craniosynostosis indicates MGS7. Combination of 2D and 3D ultrasonography helps to detect craniosynostosis. The affected fetus was confirmed a compound heterozygote of CDC45 related MGS by whole-exome sequencing, which is critical in identifying rare genetic diseases.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

Screening and Analysis of the Marker Components in Ganoderma lucidum by HPLC and HPLC-MSn with the Aid of Chemometrics.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. The present study was to establish a fingerprint evaluation system based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) for the identification and quality control of G. lucidum. Fifteen samples from the Chinese provinces of Hainan, Neimeng, Shangdong, Jilin, Anhui, Henan, Yunnan, Guangxi and Fujian were analyzed by HPLC-PAD and HPLC-MSn. Forty-seven compounds were detected by HPLC, of which forty-two compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. Ganoderic acid B, 3,7,15-trihydroxy-11,23-dioxolanost-8,16-dien-26-oic acid, lucidenic acid A, ganoderic acid G, and 3,7-oxo-12-acetylganoderic acid DM were deemed to be the marker compounds to distinguish the samples with different quality according to both CA and PCA. This study provides helpful chemical information for further research on the anti-tumor activity and mechanism of action of G. lucidum. The results proved that fingerprints combined with chemometrics are a simple, rapid and effective method for the quality control of G. lucidum.

Quality Evaluation and Chemical Markers Screening of Salvia miltiorrhiza Bge. (Danshen) Based on HPLC Fingerprints and HPLC-MSn Coupled with Chemometrics.

Danshen, the dried root of Salvia miltiorrhiza Bge., is a widely used commercially available herbal drug, and unstable quality of different samples is a current issue. This study focused on a comprehensive and systematic method combining fingerprints and chemical identification with chemometrics for discrimination and quality assessment of Danshen samples. Twenty-five samples were analyzed by HPLC-PAD and HPLC-MSn. Forty-nine components were identified and characteristic fragmentation regularities were summarized for further interpretation of bioactive components. Chemometric analysis was employed to differentiate samples and clarify the quality differences of Danshen including hierarchical cluster analysis, principal component analysis, and partial least squares discriminant analysis. Consistent results were that the samples were divided into three categories which reflected the difference in quality of Danshen samples. By analyzing the reasons for sample classification, it was revealed that the processing method had a more obvious impact on sample classification than the geographical origin, it induced the different content of bioactive compounds and finally lead to different qualities. Cryptotanshinone, trijuganone B, and 15,16-dihydrotanshinone I were screened out as markers to distinguish samples by different processing methods. The developed strategy could provide a reference for evaluation and discrimination of other traditional herbal medicines.

Structure Identification and Anti-Cancer Pharmacological Prediction of Triterpenes from Ganoderma lucidum.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, which is a popularly used traditional Chinese medicine for complementary cancer therapy. In the present study, systematic isolation, and in silico pharmacological prediction are implemented to discover potential anti-cancer active GTs from G. lucidum. Nineteen GTs, three steroids, one cerebroside, and one thymidine were isolated from G. lucidum. Six GTs were first isolated from the fruiting bodies of G. lucidum, including 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid methyl ester (1), 3ß,7ß,15ß-trihydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (2), 3ß,7ß,15α,28-tetrahydroxy-11,23-dioxo-lanost-8,16-dien-26-oic acid (3), ganotropic acid (4), 26-nor-11,23-dioxo-5α-lanost-8-en-3ß,7ß,15α,25-tetrol (5) and (3ß,7α)-dihydroxy-lanosta-8,24-dien- 11-one (6). (4E,8E)-N-d-2'-hydroxypalmitoyl-l-O-ß-d-glucopyranosyl-9-methyl-4,8-spingodienine (7), and stigmasta-7,22-dien-3ß,5α,6α-triol (8) were first reported from the genus Ganodema. By using reverse pharmacophoric profiling of the six GTs, thirty potential anti-cancer therapeutic targets were identified and utilized to construct their ingredient-target interaction network. Then nineteen high frequency targets of GTs were selected from thirty potential targets to construct a protein interaction network (PIN). In order to cluster the pharmacological activity of GTs, twelve function modules were identified by molecular complex detection (MCODE) and gene ontology (GO) enrichment analysis. The results indicated that anti-cancer effect of GTs might be related to histone acetylation and interphase of mitotic cell cycle by regulating general control non-derepressible 5 (GCN5) and cyclin-dependent kinase-2 (CDK2), respectively. This research mode of extraction, isolation, pharmacological prediction, and PIN analysis might be beneficial to rapidly predict and discover pharmacological activities of novel compounds.

Screening and Analysis of the Potential Bioactive Components of Poria cocos (Schw.) Wolf by HPLC and HPLC-MS(n) with the Aid of Chemometrics.

The aim of the present study was to establish a new method based on Similarity Analysis (SA), Cluster Analysis (CA) and Principal Component Analysis (PCA) to determine the quality of different samples of Poria cocos (Schw.) Wolf obtained from Yunnan, Hubei, Guizhou, Fujian, Henan, Guangxi, Anhui and Sichuan in China. For this purpose 15 samples from the different habitats were analyzed by HPLC-PAD and HPLC-MS(n). Twenty-three compounds were detected by HPLC-MS(n), of which twenty compounds were tentatively identified by comparing their retention times and mass spectrometry data with that of reference compounds and reviewing the literature. The characteristic fragmentations were summarized. 3-epi-Dehydrotumulosic acid (F13), 3-oxo-16α,25-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F4), 3-oxo-6,16α-dihydroxylanosta-7,9(11),24(31)-trien-21-oic acid (F7) and dehydropachymic acid (F15) were deemed to be suitable marker compounds to distinguish between samples of different quality according to CA and PCA. This study provides helpful chemical information for further anti-tumor activity and active mechanism research on P. cocos. The results proved that fingerprint combined with a chemometric approach is a simple, rapid and effective method for the quality discrimination of P. cocos.

[Research progress on salvianolic acids of Salvia miltiorrhiza].

Salvia miltiorrhiza is one of the most common traditional Chinese medicines. It has rich resources in China. According to modern studies, phenolic acids are the main effective components in S. miltiorrhiza. These components have cardiovascular and cerebrovascular protective effect, and anti-tumor, antioxidant, anti-inflammatory, and antifibrotic activities, etc. It has been widely used for the treatment of cardiovascular and cerebrovascular diseases and others. In this paper, the chemicals and pharmacological effects of phenolic acids from S. miltiorrhiza were summarized in the last decade. Its researches and development prospects were also analyzed for further studying and comprehensive utilization of these phenolic acids.

Fructus phyllanthi tannin fraction induces apoptosis and inhibits migration and invasion of human lung squamous carcinoma cells in vitro via MAPK/MMP pathways.

AIM: Fructus phyllanthi tannin fraction (PTF) from the traditional Tibetan medicine Fructus phyllanthi has been found to inhibit lung and liver carcinoma in mice. In this study we investigated the anticancer mechanisms of PTF in human lung squamous carcinoma cells in vitro. METHODS: Human lung squamous carcinoma cell line (NCI-H1703), human large-cell lung cancer cell line (NCI-H460), human lung adenocarcinoma cell line (A549) and human fibrosarcoma cell line (HT1080) were tested. Cell viability was detected with MTT assay. Cell migration and invasion were assessed using a wound healing assay and a transwell chemotaxis chambers assay, respectively. Cell apoptosis was analyzed with flow cytometric analysis. The levels of apoptosis-related and metastasis-related proteins were detected by Western blot and immunofluorescence. RESULTS: PTF dose-dependently inhibited the viability of the 3 human lung cancer cells. The IC50 values of PTF in inhibition of NCI-H1703, NCI-H460, and A549 cells were 33, 203, and 94 mg/L, respectively. PTF (15, 30, and 60 mg/L) dose-dependently induced apoptosis of NCI-H1703 cells. Treatment of NCI-H1703 and HT1080 cells with PTF significantly inhibited cell migration, and reduced the number of invasive cells through Matrigel. Furthermore, PTF dose-dependently down-regulated the expression of phosphor-ERK1/2, MMP-2 and MMP-9, up-regulated the expression of phosphor-JNK, but had no significant effect on the expression of ERK1/2 or JNK. CONCLUSION: PTF induces cell apoptosis and inhibits the migration and invasion of NCI-H1703 cells by decreasing MPPs expression through regulation of the MAPK pathway.

A comprehensive review of the structure elucidation and biological activity of triterpenoids from Ganoderma spp.

Ganoderma triterpenes (GTs) are the major secondary metabolites of Ganoderma lucidum, a traditional Chinese medicine, popularly used for complementary cancer therapy. GTs are lanostane-tetracyclic triterpenes. They have been reported to possess anti-tumor, anti-inflammation, antioxidant, antimicrobial and blood fat reducing effects. To date, 316 GTs have been found and their similar chemical structures have proved difficult to elucidate. This paper compiles 316 naturally occurring triterpenes from Ganoderma based on the literature published through January 2013 along with their structures, physiological activities and 13C-NMR spectral data.

[HPLC-fingerprint-based quality evaluation on a Tibetan medicine Phyllanthus emblica and its tannin parts].

This study is to establish the fingerprint for Phyllanthus emblica and their tannin parts from different habitats by HPLC for its quality control. The determination was carried out on a Diamonsil C18 (4.6 mm x 250 mm, 5 microm) column, with methanol-0.2% glacial acetic acid as mobile phase with gradient elution at a flow rate of 1 mL x min(-1). The temperature was maintained at 30 degrees C and the detected wavelength is 260 nm, Thirteen chromatographic peaks were extracted as the common peaks of the fingerprint of P. emblica, and eleven as the common peaks of P. emblica tannin parts, and five peaks were identified by comparing with referent samples. The fingerprints of 8 samples were compared and classified by similarity evaluation, cluster analysis and principal component analysis (PCA). The similarity degrees of eight P. emblica were between 0.763 and 0.993, while tannin parts were between 0.903 and 0.991. All the samples of P. emblica and their tannin parts were classified into 3 categories. The method was so highly reproducible, simple and reliable that it could provide basis for quality control and evaluation of P. emblica from different habitats.

Tannins in Phyllanthus emblica L. improves cisplatin efficacy in lung cancer cells by boosting endoplasmic reticulum stress to trigger immunogenic cell death.

BACKGROUND: Lung cancer is one of the deadliest cancers world-wide and immunotherapy has been considered as a promising therapeutic strategy. Previously, our study found that tannins in Phyllanthus emblica L. (PTF) could inhibit the growth of tumor by activating the immune response in liver cancer, and also exhibited a cytotoxicity on human lung cancer cells A549, H460, H1703 in vitro. OBJECTIVE: To explore whether PTF inhibited the growth of lung cancer through its immune-regulating function and to clarify underlying mechanisms. METHODS: The induction of immunogenic cell death (ICD) were characterized by calreticulin exposure, extracellular ATP secretion, and High Mobility Group Box 1(HMGB1) release both in vivo using LLC-derived xenograft tumor model and in vitro using both mouse LLC and human A549 cancer cells. RESULTS: PTF inhibited lung cancer cells growth and tumorigenesis in vivo/vitro and promoted anti-tumor immune responses. We further found that PTF could induce ICD, which then activated Type I interferon responses and CXCL9/10-mediated chemotaxis. Mechanistically, PTF induced the formation of intracellular protein aggregates and following activation of PERK/ATF4/CHOP-dependent endoplasmic reticulum stress-related ICD. Moreover, PTF improved the antitumor efficacy of cisplatin by inducing ICD both in vitro and in vivo. Finally, we screened out 5 components from PTF, including gallocatechin, gallic acid, methyl gallate, ethyl gallate and ellagic acid, which could induce ICD in vitro and might be considered as the potential antitumor pharmacodynamic substances. CONCLUSION: In conclusion, PTF inhibits the growth of lung cancer by triggering ICD and remodeling the tumor microenvironment, suggesting that PTF may have promising prospects as an adjacent immunotherapy for cancers.

Human Amniotic Fluid Stem Cells Exert Immunosuppressive Effects on T Lymphocytes in Allergic Rhinitis.

AIM: The study aims to investigate the immunomodulatory effect of Amniotic fluid stem (AFS) cells to Th2-skewed allergic rhinitis (AR) on T-lymphocyte proliferation, viability, activation and cytokine production. BACKGROUND: AFS cells can suppress peripheral blood mononuclear cells (PBMCs) proliferation and display immunomodulatory properties, but AFS cells' immunoregulation on AR has not been defined. METHODS: Human AFS cells were derived from magnetic cell sorting and co-cultured with PBMCs from AR patients stimulated by phytohemagglutinin (PHA). The AFS cells-associated suppressive proliferation was analyzed using CellTrace™ Violet assay; the T lymphocytes proliferation, viability, activation and the Foxp3+ Treg cells were determined by flow cytometry; cytokine levels were measured using an enzyme- linked immunosorbent assay. RESULTS: We determined that AFS cells significantly inhibited PHA-induced CD3+ T lymphocyte proliferation at the ratio higher than 1:50 (AFS cells: PBMCs) (P<0.05); AFS cells obviously increased the T lymphocytes viability (P<0.01), inhibited the apoptosis of T lymphocytes (P<0.001), compared to PBMCs alone; AFS cells suppressed CD3+CD25+ T lymphocytes activated by PHA (P<0.05); AFS cells significantly promote Treg cells expansion in house dust mite (HDM)-stimulated PBMCs from AR patients (P<0.05). Compared with HDM-stimulated PBMCs, AFS cell co-culture predominantly decreased IL-4 level (P<0.05), but increased IFN-γ and IL-10 levels (P<0.01). CONCLUSION: AFS cells modulate the T-cells' immune imbalance towards Th2 suppression in AR, which can be used as a new cell banking for allergic airway diseases.

Enhanced TSG stability through co-assembly with C3G: the mechanism behind processing Polygonum multiflorum Thunb with black beans via supramolecular analysis.

Elucidating the underlying mechanism of the processing of Chinese herbal medicine (CHM) is crucial and also challenging for the modernization of Traditional Chinese Medicine (TCM). Herein, inspired by the traditional method for processing the Chinese herb Polygonum multiflorum (PM) Thunb with excipient black beans, the representative herbal components trans-2,3,5,4'-tetrahydroxystilbene 2-O-ß-D-glucopyranoside (TSG) and cyanidin-3-O-ß-glucoside (C3G) from each herbal medicine were selected to investigate the processing mechanism at the supramolecular level. The co-assemblies of TSG/C3G were found to be formed, and their structure was characterized by electronic microscopy and a small angle X-ray scattering (SAXS) technique. In addition, the supramolecular interactions between TSG and C3G were fully probed with UV-Vis, fluorescence, XRD, and NMR spectroscopy. Molecular dynamics were further performed to simulate the assembly processes of TSG and C3G. Notably, the formation of TSG/C3G co-assemblies was found to significantly enhance the stability of TSG against light, Fe3+, and simulated intestinal fluids. The co-assembly of TSG and C3G that leads to supramolecular aggregates discovered here may imply the underlying mechanism of processing PM with black beans. Our results may also suggest that a new effective form of TCM is supramolecular aggregates rather than each component.

Correction: Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Correction for 'Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration' by Shukai Wang et al., Food Funct., 2023, 14, 4607-4620, https://doi.org/10.1039/D2FO03685A.

Moringa oleifera leaf polysaccharides exert anti-lung cancer effects upon targeting TLR4 to reverse the tumor-associated macrophage phenotype and promote T-cell infiltration.

Tumor-associated macrophages (TAMs) participate in tumorigenesis, growth, invasion as well as metastasis by facilitating an immunosuppressive tumor microenvironment. Reversing the pro-tumoral M2 phenotype of TAMs has become a hot spot in advancing cancer immunotherapy. In the current study, the content of Moringa oleifera leaf polysaccharides (MOLP) was determined and characterized, along with the anti-cancer mechanism of MOLP studied in a Lewis lung cancer (LLC) tumor-bearing mouse model and bone marrow-derived macrophages. The monosaccharide composition and gel permeation chromatography analyses show that MOLP are mainly composed of galactose, glucose, and arabinose, with approximately 17.35 kDa average molecular weight (Mw). In vivo studies demonstrate that MOLP convert TAMs from the immunosuppressive M2 phenotype to the antitumor M1 phenotype, thus inducing CXCL9 and CXCL10 expression and increasing T-cell infiltration in the tumor. Furthermore, macrophage depletion and T cell suppression demonstrated that the tumor suppressive effect of MOLP was reliant on reprogramming macrophage polarization and T cell infiltration. In vitro studies revealed that MOLP could induce the phenotypic switch from M2 macrophages to M1 by targeting TLR4. The current study highlights that MOLP are promising anticancer plant-derived polysaccharides with potential in modulating the immune microenvironment and have a bright application prospect in the immunotherapy of lung cancer.

Association between short inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.

OBJECTIVE: To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery. METHODS: This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery. RESULTS: Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26). CONCLUSIONS: The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.

Tannins in Terminalia bellirica inhibits hepatocellular carcinoma growth via re-educating tumor-associated macrophages and restoring CD8+T cell function.

Tumor-associated macrophages (TAMs) are the major immunosuppressive components infiltrating the tumor microenvironment (TME). Targeting TAMs has emerged as a promising strategy to remodel immunosuppressive TME and enhance T-cell mediated anti-tumor immunity for cancer therapy. In this study, we investigate the effect and mechanism of total tannin fraction of Terminalia bellirica (Gaertn.) Roxb. (TB-TF) against hepatocellular carcinoma (HCC) using established Hepa1-6 orthotopic mouse model and murine bone marrow derived macrophage polarization model. Here we showed that TB-TF significantly inhibited orthotopic tumor growth and promoted the polarization of M2-TAMs toward the anti-tumor M1 phenotype in vivo. Further studies showed that TB-TF reversed tumor-conditioned medium induced M2 polarization of macrophages as indicated by increased expression of TNF-α, IL-1ß, and iNOS, and decreased expression of Arg-1, thereby re-educating macrophages co-cultured with tumor-conditioned medium into M1 phenotype. In addition, we found that TB-TF also promoted T cell infiltration mediated by chemokines such as CCL5 and CXCL10, and restored the cytotoxic function of CD8+T cells as evidenced by upregulated expression of Granzyme B, Perforin, and IFN-γ. Our data suggest TB-TF as a promising anti-cancer agent, mediates its anti-tumor effects via remodeling the tumor immunosuppressive microenvironment, indicating its potential in the immunotherapy for hepatocellular carcinoma.