Microbiome-Metabolomic Analysis Revealed the Immunoprotective Effects of the Extract of Vanilla planifolia Andrew (EVPA) on Immunosuppressed Mice.

This study investigated the immunoprotective effects of the extract of Vanilla planifolia Andrew (EVPA) on cyclophosphamide (Cy)-induced immunosuppression in mice. The results show that EVPA administration significantly alleviated the immune damage induced by Cy, as evidenced by an improved body weight, organ index, and colonic injury. A further analysis of microbial diversity revealed that the EVPA primarily increased the abundance of the beneficial bacteria Verrucomicrobiota, Lactobacillaceae, and Lactobacillus while decreasing Akkermansiaceae, Akkermansia, Romboutsia, and Lactococcus, thereby ameliorating the microbial dysbiosis caused by Cy. A metabolomic analysis revealed significant alterations in the microbial metabolite levels after EVPA treatment, including urobilinogen, formamidopyrimidine nucleoside triphosphate, Cer (d18:1/18:0), pantetheine, and LysoPC (15:0/0:0). These altered metabolites are associated with pathways related to sphingolipid metabolism, carbapenem biosynthesis, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, and porphyrin metabolism. Furthermore, significant correlations were observed between certain microbial groups and the differential metabolites. These findings provide new insights into the immunomodulatory effects of EVPA on the intestinal microbiota and metabolism, laying the foundation for more extensive utilization.

Identification of fibroblast-related genes based on single-cell and machine learning to predict the prognosis and endocrine metabolism of pancreatic cancer.

Background: Single-cell sequencing technology has become an indispensable tool in tumor mechanism and heterogeneity studies. Pancreatic adenocarcinoma (PAAD) lacks early specific symptoms, and comprehensive bioinformatics analysis for PAAD contributes to the developmental mechanisms. Methods: We performed dimensionality reduction analysis on the single-cell sequencing data GSE165399 of PAAD to obtain the specific cell clusters. We then obtained cell cluster-associated gene modules by weighted co-expression network analysis and identified tumorigenesis-associated cell clusters and gene modules in PAAD by trajectory analysis. Tumor-associated genes of PAAD were intersected with cell cluster marker genes and within the signature module to obtain genes associated with PAAD occurrence to construct a prognostic risk assessment tool by the COX model. The performance of the model was assessed by the Kaplan-Meier (K-M) curve and the receiver operating characteristic (ROC) curve. The score of endocrine pathways was assessed by ssGSEA analysis. Results: The PAAD single-cell dataset GSE165399 was filtered and downscaled, and finally, 17 cell subgroups were filtered and 17 cell clusters were labeled. WGCNA analysis revealed that the brown module was most associated with tumorigenesis. Among them, the brown module was significantly associated with C11 and C14 cell clusters. C11 and C14 cell clusters belonged to fibroblast and circulating fetal cells, respectively, and trajectory analysis showed low heterogeneity for fibroblast and extremely high heterogeneity for circulating fetal cells. Next, through differential analysis, we found that genes within the C11 cluster were highly associated with tumorigenesis. Finally, we constructed the RiskScore system, and K-M curves and ROC curves revealed that RiskScore possessed objective clinical prognostic potential and demonstrated consistent robustness in multiple datasets. The low-risk group presented a higher endocrine metabolism and lower immune infiltrate state. Conclusion: We identified prognostic models consisting of APOL1, BHLHE40, CLMP, GNG12, LOX, LY6E, MYL12B, RND3, SOX4, and RiskScore showed promising clinical value. RiskScore possibly carries a credible clinical prognostic potential for PAAD.

Zinc Deficiency Exacerbates Behavioral Impediments and Dopaminergic Neuron Degeneration in a Mouse Model of Parkinson Disease.

BACKGROUND: Circulating zinc (Zn) concentrations are lower than normal in patients with Parkinson disease (PD). It is unknown whether Zn deficiency increases the susceptibility to PD. OBJECTIVES: The study aimed to investigate the effect of dietary Zn deficiency on behaviors and dopaminergic neurons in a mouse model of PD and to explore potential mechanisms. METHODS: Male C57BL/6J mice aged 8-10 wk were fed Zn adequate (ZnA; 30 µg/g) or Zn deficient (ZnD; <5 µg/g) diet throughout the experiments. Six weeks later 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected to generate the PD model. Controls were injected with saline. Thus, 4 groups (Saline-ZnA, Saline-ZnD, MPTP-ZnA, and MPTP-ZnD) were formed. The experiment lasted 13 wk. Open field test, rotarod test, immunohistochemistry, and RNA sequencing were performed. Data were analyzed with t-test, 2-factor ANOVA, or Kruskal-Wallis test. RESULTS: Both MPTP and ZnD diet treatments led to a significant reduction in blood Zn concentrations (PMPTP = 0.012, PZn = 0.014), reduced total distance traveled (PMPTP < 0.001, PZn = 0.031), and affected the degeneration of dopaminergic neurons in the substantia nigra (PMPTP < 0.001, PZn = 0.020). In the MPTP-treated mice, the ZnD diet significantly reduced total distance traveled by 22.4% (P = 0.026), decreased latency to fall by 49.9% (P = 0.026), and reduced dopaminergic neurons by 59.3% (P = 0.002) compared with the ZnA diet. RNA sequencing analysis revealed a total of 301 differentially expressed genes (156 upregulated; 145 downregulated) in the substantia nigra of ZnD mice compared with ZnA mice. The genes were involved in a number of processes, including protein degradation, mitochondria integrity, and α-synuclein aggregation. CONCLUSIONS: Zn deficiency aggravates movement disorders in PD mice. Our results support previous clinical observations and suggest that appropriate Zn supplementation may be beneficial for PD.

Endoscopic Fenestration for Treating Galassi Type III Middle Cranial Fossa Arachnoid Cysts: Single- and Multiple-stoma have the Same Curative Effect.

BACKGROUND: For endoscopic fenestration of middle cranial fossa arachnoid cysts (MCFACs), the decisions on the location and number of stomas are key issues. However, research on this particular topic has been limited. Thus, this study aimed to compare single- versus multiple-stoma endoscopic fenestration for treating Galassi type III MCFACs. METHODS: This retrospective study included 86 patients with Galassi type III MCFACs treated with endoscopic fenestration. Single-stoma fenestration to the basal cistern was performed in 37 cases, whereas multiple-stoma fenestration to the basal cistern and the carotid cistern was performed in 49 cases. Clinicoradiologic profiles and follow-up data were analyzed. RESULTS: The rate of symptom relief was 83.7% (72/86), and the rate of cyst shrinkage was 96.5% (83/86). Postoperative ipsilateral subdural effusion, which was significant (p = 0.042), and noninfectious fever were the two most common complications in the single- and multiple-stoma groups. No significant differences in intraoperative nerve injury, vascular injury, proportion of cases with cyst reduction, and symptom remission rate were observed between the two groups. The rates of cyst recurrence and secondary surgery in the single-stoma group were higher than those in the multiple-stoma group, although the difference was not significant. CONCLUSION: Endoscopic fenestration is an effective and minimally invasive approach for treating Galassi type III MCFACs. Single- and multiple-stoma endoscopic fenestrations have the same curative effect.

Comparison on volatile components between Artemisiae Verlotori Folium and Artemisiae Argyi Folium based on GC-MS and chemometrics / 中国中药杂志

Artemisiae Argyi Folium is commonly used in clinical practice. Artemisiae Verlotori Folium, the dried leaves of Artemisia verlotorum, is often used as a folk substitute for Artemisiae Argyi Folium in Lingnan area. In this study, gas chromatography-triple quadrupole mass spectrometry(GC-MS) was used to detect the volatile oil components of 27 samples of Artemisiae Verlotori Folium and 13 samples of Artemisiae Argyi Folium, and the volatile components were compared between the two species. The internal standard method was combined with multi-reaction monitoring mode(MRM) to determine the content of six major volatile components. Hierarchical clustering analysis(HCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the content data. The results showed that the Artemisiae Argyi Folium samples had higher content and more abundant volatile oils than the Artemisiae Verlotori Folium samples. Artemisiae Argyi Folium mainly had the components with lower boiling points, while Artemisiae Verlotori Folium mainly had the components with higher boiling points. Terpenoids were the main volatile components in Artemisiae Verlotori Folium(mainly sesquiterpenoids) and Artemisiae Argyi Folium(monoterpenoids). In addition, Artemisiae Argyi Folium had higher content of oxygen-containing derivatives than Artemisiae Verlotori Folium. Furthermore, the stoichiometric analysis showed that the two species could be distinguished by both HCA and OPLS-DA, indicating that the volatile components of the two were significantly different. This study can provide a scientific basis for the quality evaluation and data support for the local rational application of Artemisiae Verlotori Folium in Lingnan.

Expression Pattern and Prognostic Value of CTLA-4, CD86, and Tumor-Infiltrating Lymphocytes in Rectal Cancer after Neoadjuvant Chemo(radio)therapy.

The synergistic effect of combining immune checkpoint inhibitors (ICIs) with neoadjuvant chemo(radio)therapy (nCRT) in colorectal cancer is still limited. We aimed to understand the impact of nCRT on the tumor microenvironment and to explore favorable immune markers of this combination. Herein, we investigated the expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), CD86, CD4, and CD8 after nCRT and its association with clinicopathological characteristics. Immunostaining of immune-related molecules was performed in 255 surgically resected specimens from rectal cancer patients treated with nCRT. CD4 and CD8 expression on the tumor (tCD4/CD8), stroma (sCD4/CD8), and invasive front (iCD4/CD8) was evaluated. The expression levels of immune-related molecules were significantly lower in the nCRT-treated group, except for CTLA-4 and sCD8. However, patients with higher sCD8+ cell density and CTLA-4 expression had better progression-free survival (PFS) and distant metastasis-free survival (DMFS). In addition, higher CD86 expression was associated with poorer overall survival (OS). Higher CTLA-4 expression was associated with higher tCD8+ cell density, whereas CD86 expression was correlated with the cell density of t/sCD8. Prognostic analysis confirmed that the relationships between CTLA-4 and DMFS as well as CD86 and OS were significantly correlated in low rather than high CD8+ cell density. Further the combination of CD8+ cell density and CD86 expression was shown to be an independent prognostic factor of OS, whereas the combination of CTLA-4 was not for DMFS. Together, these results demonstrate significant correlations between CD86 expression and t/sCD8+ cell density in rectal cancer after nCRT and could potentially have clinical implications for combining ICIs and nCRT.

[Spatiotemporal distribution and multi-source characteristics of microplastics in the soil and water environment of Poyang Lake Wetland, China]. / 鄱阳湖湿地水土环境中微塑料的时空分布及多源性.

The increasing microplastics (MPs) pollution in freshwater wetlands has received global concerns. To investigate the spatiotemporal dynamics of MPs in the wetlands of Poyang Lake, surface water and sediment samples were collected from five rivers entering the lake as well as the confluence of Poyang Lake into the Yangtze River, in both dry and wet seasons. The MPs in water and sediment were extracted by the digestion-filtration method and flotation-separation-digestion-filtration method, respectively. Light microscope, Fourier transform infrared spectroscopy, and scanning electron microscope were used for microplastic characterization. The results showed that the abundance of MPs ranged from 32.1 to 127.3 n·L-1 in water samples, and from 533.3 to 1286.6 n·kg-1 in sediment samples during the wet season. In the dry season, the abundance of MPs ranged from 87.1 to 295.5 n·L-1 in water and from 460.0 to 1368.0 n·kg-1 in sediment. Compared with other freshwater wetlands, Poyang Lake had higher abundance of MPs. There were temporal and spatial differences among regions. The main forms of MPs included beads, fragment, film and fiber, and the corresponding polymer components were mainly polystyrene, polypropy-lene and polyethylene. Beads (35.7% in wet season and 52.0% in dry season) were the main form of MPs in water, while fragment (45.8% in wet season and 69.7% in dry season) was the main form of MPs in sediment. Small size (<0.1 mm) MPs were dominant (>50%) in water and sediment in both seasons. The abundance of MPs with different sizes decreased with the increases of size. The potential main sources of MPs in the wetlands of Poyang Lake included the discharge of industrial wastewater, discharge from urban and rural domestic sewage treatment plants, agricultural and fishing activities, and improper disposal of domestic wastes.

Identification and Verification of SLC27A1, PTBP1 and EIF5A With Significantly Altered Expression in Aggressive Pituitary Adenomas.

Background: Aggressive pituitary adenoma encircling the internal carotid artery has a poor clinical prognosis because of a high surgical risk and a high recurrence rate. This seriously affects patients' quality of life and yet there is no effective medical treatment. The European Diagnostic Guidelines have recommended the use of temozolomide (TMZ) for these aggressive pituitary adenomas, but the treatment remission rate has been less than 50%. Methods: In this study, transcriptome sequencing of pituitary tumour tissues and TMZ-treated pituitary tumour cell lines were employed to explore the significance gene expressions affecting the efficacy of TMZ treatment for pituitary tumours. To clarify the roles of these gene expressions, six adult patients with pituitary adenomas treated in Tiantan Hospital from 2015 to 2020 and a pituitary adenoma cell line (Att20 sensitive to TMZ treatment) were analyzed by mRNA transcriptome sequencing. The differentially expressed genes were assayed by analyzing the sequencing results, and the expression level of these genes was further verified by immunohistochemistry. In addition, Ki67, VEGF, and p53 of the tumour tissues were also verified by immunohistochemistry. Results: In tumour tissues, mRNA sequencing showed that PTBP1 and EIF5A were significantly overexpressed in primary pituitary adenomas and SLC27A1 was significantly overexpressed in aggressive pituitary adenomas. Also in the pituitary adenoma cell line (AtT20), SLC27A1 expression levels were suppressed by TMZ treatment. Subsequent immunohistochemistry confirmed the sequencing results. Conclusion: High expression of SLC27A1 and low expression of EIF5A and PTBP1 may be potential indicators to predict the progression of aggressive pituitary adenomas, and patients with high SLC27A1 subtype may be sensitive to TMZ in clinical treatments.

Long non-coding RNA ANRIL promotes chemoresistance in triple-negative breast cancer via enhancing aerobic glycolysis.

AIMS: lncRNA ANRIL expression is dysregulated in many human cancers and is thus a useful prognostic marker for cancer patients. However, whether ANRIL is involved in drug resistance in triple-negative breast cancer (TNBC) has not yet been investigated. MAIN METHODS: A luciferase reporter assay was conducted to verify the binding between miR-125a and ANRIL. RT-PCR and western blotting were performed to detect the expression of miR-125a, ANRIL, and ENO1. Glycolysis stress was assessed using the Seahorse extracellular flux analyzer. Functional studies were performed using both in vitro and in vivo xenograft models. KEY FINDINGS: ANRIL was markedly upregulated in both patients with TNBC and TNBC cell lines. Knockdown of ANRIL increased the cytotoxic effect of ADR and repressed cellular glycolytic activity in TNBC cells. Mechanistic analysis showed that ANRIL may act as a competing endogenous RNA of miR-125a to relieve the repressive effect of miR-125a on its target glycolytic enzyme enolase (ENO1). Notably, 2-deoxy-glucose attenuated ANRIL-induced increase in drug resistance in TNBC cells. SIGNIFICANCE: These results indicate that knockdown of ANRIL plays an active role in overcoming drug resistance in TNBC by inhibiting glycolysis through the miR-125a/ENO1 pathway, which may be useful for the development of novel therapeutic targets for treating patients with TNBC, especially those with drug resistance.

ZKSCAN5 Activates VEGFC Expression by Recruiting SETD7 to Promote the Lymphangiogenesis, Tumour Growth, and Metastasis of Breast Cancer.

The growth of lymphatic vessels (lymphangiogenesis) plays a pivotal role in breast cancer progression and metastasis and the immune response. Vascular endothelial growth factor C (VEGFC) has been demonstrated to accelerate cancer metastasis and modulate the immune system by enhancing lymphangiogenesis. However, it remains largely unclear how transcription factors physically regulate VEGFC expression by interacting with histone-modifying enzymes. Like many histone-modifying enzymes, SETD7 plays a key role in cell proliferation and inhibits tumour cell differentiation. In this study, we identified the role of the transcription factor zinc finger with KRAB and SCAN domains 5 (ZKSCAN5) in interacting with histone methyltransferase SETD7 and mediating VEGFC transcription and tumour lymphangiogenesis. ZKSCAN5 interacts with and recruits SETD7 to the VEGFC promoter. By regulating breast cancer-secreted VEGFC, ZKSCAN5 could induce the tube formation of lymph endothelial cells, which promotes tumour proliferation, migration, and metastasis. Clinically, the expression of ZKSCAN5 was frequently upregulated in patients with breast cancer and positively correlated with the expression of VEGFC and the number of lymphatic microvessels. ZKSCAN5 is a poor prognostic factor for patients with breast cancer. Our results characterise the role of ZKSCAN5 in regulating VEGFC transcription and predict ZKSCAN5 as a breast cancer therapeutic target.

STAT3/LINC00671 axis regulates papillary thyroid tumor growth and metastasis via LDHA-mediated glycolysis.

Lactate dehydrogenase A (LDHA), a critical component of the glycolytic pathway, relates to the development of various cancers, including thyroid cancer. However, the regulatory mechanism of LDHA inhibition and the physiological significance of the LDHA inhibitors in papillary thyroid cancer (PTC) are unknown. Long non-coding RNA (lncRNA) plays a vital role in tumor growth and progression. Here, we identified a novel lncRNA LINC00671 negatively correlated with LDHA, downregulating LDHA expression and predicting good clinical outcome in thyroid cancer. Moreover, hypoxia inhibits LINC00671 expression and activates LDHA expression largely through transcriptional factor STAT3. STAT3/LINC00671/LDHA axis regulates thyroid cancer glycolysis, growth, and lung metastasis both in vitro and in vivo. In thyroid cancer patients, LINC00671 expression is negatively correlated with LDHA and STAT3 expression. Our work established STAT3/LINC00671/LDHA as a critical axis to regulate PTC growth and progression. Inhibition of LDHA or STAT3 or supplement of LINC00671 could be potential therapeutic strategies in thyroid cancer.

Clinical features, radiological profiles, pathological features and surgical outcomes of pituicytomas: a report of 11 cases and a pooled analysis of individual patient data.

BACKGROUND: Pituicytoma is an extremely rare low-grade glial tumor that is closely related to the neurohypophysis axis. Most studies of pituicytomas include only several cases. To better understand this disease, we reviewed a series of cases of pituicytomas. The diagnosis and treatment of pituicytoma must be further elucidated. METHODS: Eleven patients with pituicytoma admitted to Beijing Tiantan Hospital from 2012 to 2019 were selected. The clinical features, including radiological and histological examination, surgical records and prognosis were reviewed. Sixty-eight other previously published cases of pituicytoma also were used to analyze the predictive factors for the results. The Cox regression model was used for univariate and multivariate analyses. RESULTS: Our patients included 5 males (45.5%) and 6 females (54.5%), with a mean age of 49.3 years. The tumor was located in the suprasellar region in 5 patients (45.5%), intrasellar region in 4 patients (36.4%), and intrasellar-suprasellar region in 2 patients (18.2%). All patients were misdiagnosed with other common tumors in the sellar region before the operation. During the operation, gross total resection (GTR) of the tumor was achieved in 6 patients (54.5%), and subtotal resection (STR) was achieved in 5 patients (45.5%). The mean progression-free survival (PFS) time was 29.82 months. Tumor progression after surgical resection occurred in 4 patients (36.4%). Among them, 60.0% of the patients (cases 4, 5, 7) with STR experienced progression, while 16.7% of the patients (case 2) with GTR experienced progression. Combined with the 68 cases in the literature, GTR was an independent risk factor for PFS time (P < 0.05). CONCLUSIONS: Pituicytomas are more common in middle-aged people and the sellar region. The clinical manifestations of pituicytomas are different, but no diagnostic clinical features have been identified other than an abnormally abundant blood supply. Currently, GTR is the best approach for the treatment of pituicytomas. More patients and longer follow-up periods were needed to further elucidate the biological features of pituicytomas.

LSD1-Demethylated LINC01134 Confers Oxaliplatin Resistance Through SP1-Induced p62 Transcription in HCC.

BACKGROUND AND AIMS: Oxaliplatin (OXA) is one of the most common chemotherapeutics in advanced hepatocellular carcinoma (HCC), the resistance of which poses a big challenge. Long noncoding RNAs (lncRNAs) play vital roles in chemoresistance. Therefore, elucidating the underlying mechanisms and identifying predictive lncRNAs for OXA resistance is needed urgently. METHODS: RNA sequencing (RNA-seq) and fluorescence in situ hybridization (FISH) were used to investigate the OXA-resistant (OXA-R) lncRNAs. Survival analysis was performed to determine the clinical significance of homo sapiens long intergenic non-protein-coding RNA 1134 (LINC01134) and p62 expression. Luciferase, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), and chromatin isolation by RNA purification (ChIRP) assays were used to explore the mechanisms by which LINC01134 regulates p62 expression. The effects of LINC01134/SP1/p62 axis on OXA resistance were evaluated using cell viability, apoptosis, and mitochondrial function and morphology analysis. Xenografts were used to estimate the in vivo regulation of OXA resistance by LINC01134/SP1/p62 axis. ChIP, cell viability, and xenograft assays were used to identify the demethylase for LINC01134 up-regulation in OXA resistance. RESULTS: LINC01134 was identified as one of the most up-regulated lncRNAs in OXA-R cells. Higher LINC01134 expression predicted poorer OXA therapeutic efficacy. LINC01134 activates anti-oxidative pathway through p62 by recruiting transcription factor SP1 to the p62 promoter. The LINC01134/SP1/p62 axis regulates OXA resistance by altering cell viability, apoptosis, and mitochondrial homeostasis both in vitro and in vivo. Furthermore, the demethylase, lysine specific demethylase 1 (LSD1) was responsible for LINC01134 up-regulation in OXA-R cells. In patients with HCC, LINC01134 expression was positively correlated with p62 and LSD1 expressions, whereas SP1 expression positively correlated with p62 expression. CONCLUSIONS: LSD1/LINC01134/SP1/p62 axis is critical for OXA resistance in HCC. Evaluating LINC01134 expression in HCC will be effective in predicting OXA efficacy. In treatment-naive patients, targeting the LINC01134/SP1/p62 axis may be a promising strategy to overcome OXA chemoresistance.

LncRNA MEG8 promotes TNF-α expression by sponging miR-454-3p in bone-invasive pituitary adenomas.

There are few studies on the mechanism of pituitary adenoma (PA) destroying bone. The current study aimed to investigate the role of MEG8/miR-454-3p/TNF-α in bone-invasive pituitary adenomas (BIPAs). In this study, we report that lncRNA MEG8 and TNF-α are upregulated in BIPA tissues while miR-454-3p is downregulated, which is associated with poor progression-free survival (PFS). Functional assays revealed the role of up-regulated MEG8 and down-regulated miR-454-3p in promoting bone destruction. Mechanistically, MEG8 promotes TNF-α expression by sponging miR-454-3p, which ultimately leads to the occurrence of bone destruction. The mechanism is confirmed in vivo and in vitro. Therefore, our data illustrated a new regulatory mechanism of MEG8/miR-454-3p/TNF-α in BIPAs. It may provide a useful strategy for diagnosis and treatment for BIPA patients.

FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect.

Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.

Comparison of the effect of extraction methods on the quality of green coffee oil from Arabica coffee beans: Lipid yield, fatty acid composition, bioactive components, and antioxidant activity.

In this study, ultrasonic/microwave-assisted extraction (UMAE), microwave-assisted extraction (UAE), ultrasound-assisted extraction (UAE), and pressurized liquid extraction (PLE) were applied to extract green coffee oil (GCO), and the physicochemical indexes, fatty acids, tocopherols, diterpenes, and total phenols as well as antioxidant activity of GCO were investigated and compared. The results indicated that the extraction yield of UMAE was the highest (10.58 ± 0.32%), while that of PLE was the lowest (6.34 ± 0.65%), and linoleic acid and palmitic acid were the major fatty acids in the GCO, ranging from 40.67% to 43.77% and 36.57% to 38.71%, respectively. A large proportion of fatty acids and phytosterols were not significantly influenced by the four extraction techniques. However, tocopherols, diterpenes, total phenols, and the free radical scavenging activity were significantly different among these four GCOs. Moreover, structural changes in the coffee residues were explored by scanning electron microscopy and Fourier transform infrared spectroscopy. Overall, the high antioxidant activity of GCO demonstrated that it can be used as a highly economical natural product in the food and agricultural industries.

Pituitary metastasis from renal cell carcinoma: case report and review of the literature.

Pituitary metastasis(PM) from renal cell carcinoma(RCC) is rare, and is easy to be misdiagnosed. Here, we present a case of pituitary metastasis from clear-cell renal cell carcinoma(ccRCC) which was difficult to distinguish from other sellar region tumors. In addition, we systematically review the literature to find the characteristics of different tumors of the sellar region. It provides a new idea for the diagnosis of sellar region tumors in the clinic.

Supramolecular structure of Artocarpus heterophyllus Lam seed starch prepared by improved extrusion cooking technology and its relationship with in vitro digestibility.

Jackfruit seed starch (JFSS) was modified by an improved extrusion cooking technology (IECT), and the supramolecular structure, molecular weight, debranched chain length distributions, relative crystallinity (Rc), and amylose content, were studied. During IECT, the α-1.4-glycosidic bond in amylopectin was broken, which led to decreased radius of gyration (Rg), number-average molar mass (Mn), weight-average molar mass (Mw), long chains and Rc. The medium and short chains and PI (Mw/Mn) increased, while the amylose content hardly changed. The crystalline structure of JFSS was converted from A-type to V-type. Increasing the temperature and screw speed during the treatment significantly increased the medium and short chains and Rg, while it decreased the long chains, amylose, Mn, Mw, PI, and Rc. However, the opposite effect was observed when increasing the moisture content. The in vitro digestibility of JFSS was significantly improved after IECT, due to destruction of starch supramolecular structure according to principal component analysis.

Clinicopathologic significance of MYD88 L265P mutation and expression of TLR4 and P-STAT3 in primary central nervous system diffuse large B-cell lymphomas.

Patients with primary central nervous system lymphoma (PCNSL) have a prognosis poorer than that of systemic lymphoma patients. In patients with this condition, TLR4/STAT3 pathway alterations and the MYD88 L265P mutation may be viable targets for therapeutic intervention. The present study was, therefore, designed to identify clinicopathologic correlates of MYD88 mutations and TLR4/STAT3 pathway alterations in PCNSL. We detected TLR4 and p-STAT3 in 41.5% (22/53) and 43.4% (23/53) of PCNSL patients, respectively, while 60.4% of these patients (32/53) were found to harbor the MYD88 L265P mutation. TLR4 expression was found to be significantly associated with the presence of multiple brain lesions, while p-STAT3 expression was significantly linked to advanced age, the presence of multiple brain lesions, non-GCB histological findings, and non-CR status. The presence of the MYD88 L265P mutation was significantly linked to advanced age, the presence of multiple brain lesions, and DLBCL molecular subtype. Multivariate analyses additionally confirmed that elevated TLR4 and p-STAT3 expression levels are associated with a poorer PCNSL patient prognosis. Based on these findings, we hypothesize that signaling through the TLR4/MYD88/STAT3 pathway plays a key role in the pathogenesis of PCNSL.

Herbalogical study on historical evolution of collection, processing and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium / 中国中药杂志

In ancient times, the original plants of Citri Exocarpium Rubrum and Citri Grandis Exocarpium had experienced succession and change, including tangerine(Citrus reticulata), pomelo(C. grandis), and Huazhou pomelo(C. grandis 'Tomentosa'), a specific cultivar of C. grandis produced in Huazhou, Guangdong. Before the Qing Dynasty, tangerine was the main original plant, while Huazhou pomelo came to the fore in the Qing Dynasty. In the 1950 s and 1960 s, the producing area of Huazhou pomelo was destroyed, and thus it had to be supplemented with pomelo. From then on, C. grandis 'Tomentosa' and C. grandis were both listed as the original plants of Citri Grandis Exocarpium in the Chinese Pharmacopoeia. This paper reviewed the historical evolution of the collection, processing, and efficacy of Citri Exocarpium Rubrum and Citri Grandis Exocarpium. The research showed that:(1)The harvest time of the original plants of Citri Grandis Exocarpium and Citri Grandis Exocarpium had changed from maturity to immaturity. The collection and processing of Citri Exocarpium Rubrum was first recorded in the Illustrated Classics of Materia Medica in the Song Dynasty. During the Ming and Qing Dynasties, the mesocarp of Citri Exocarpium Rubrum needed to be removed completely, and Citri Grandis Exocarpium from C. grandis 'Tomentosa' was processed into different specifications such as seven-piece, five-piece, and single piece. Furthermore, processed young fruits of Huazhou pomelo appeared.(2)Citri Exocarpium Rubrum and Citri Grandis Exocarpium were processed with carp skin for the first time in the Master Lei's Discourse on Medicinal Processing. It was suggested that carp skin might be helpful for eliminating bones stuck in throat. During the Song, Jin, and Yuan Dynasties, some other processing methods such as ba-king, stir-frying, and salt-processing appeared. Honey, soil, ginger juice, and alum were firstly used as adjuvants for the processing in the Ming and Qing Dynasties. Citri Exocarpium Rubrum was mainly prepared with salt in order to improve the effect of lowering Qi, while it was unnecessary for Citri Grandis Exocarpium from C. grandis 'Tomentosa' because of its obvious effect of lowering Qi and eliminating phlegm. The stir-frying and honey-frying methods helped reduce the strong effect of Citri Grandis Exocarpium from C. grandis 'Tomentosa'.(3)According to the application of Citri Exocarpium Rubrum and Citri Grandis Exocarpium in history, their medicinal use began in Han and Tang Dynasties, developed in Song, Jin, and Yuan Dynasties, and matured in Ming and Qing Dynasties. Citri Grandis Exocarpium from C. grandis 'Tomentosa' was originally applied in Ming and Qing Dynasties, and it still plays an important in role treating COVID-19 nowadays. Moreover, Citri Grandis Exocarpium from C. grandis had cold medicinal property, while Citri Grandis Exocarpium from C. grandis 'Tomentosa' had warm medicinal property, and thus they should not be treated the same. At present, Huazhou pomelo has a certain production scale. Therefore, it is recommended that in the next edition of Chinese Pharmacopoeia, only C. grandis 'Tomentosa' should be included as the original plant of Citri Grandis Exocarpium, and C. grandis should be deleted. The results are conducive to the further development and utilization of Citri Exocarpium Rubrum and Citri Grandis Exocarpium, and support the rational use of Citri Grandis Exocarpium and its processed products.