The pretherapeutic systemic inflammation score is a prognostic predictor for elderly patients with oesophageal cancer: a case control study.

BACKGROUND: The systemic inflammation score (SIS), based on serum albumin (Alb) and lymphocyte-to-monocyte ratio (LMR), is a novel prognostic tool for some tumours. Studies indicate that the SIS can be used as a postoperative prognostic marker. However, its predictive value in elderly oesophageal squamous cell carcinoma (ESCC) patients treated with radiotherapy is unclear. METHODS: In total, 166 elderly ESCC patients who received radiotherapy with or without chemotherapy were included. Based on different combinations of Alb and LMR levels, the SIS was divided into 3 groups, SIS = 0 (n = 79), SIS = 1 (n = 71) and SIS = 2 (n = 16). The Kaplan-Meier method was used for survival analysis. Univariate and multivariate analyses were performed to assess prognosis. Time-dependent receiver operating characteristic (t-ROC) curves were used to compare the prognostic accuracy of the SIS with that of Alb, LMR, neutrophil-to lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammatory index (SII). RESULTS: Decreased Alb and LMR were both associated with shorter OS, whereas a lower SIS was significantly associated with better outcomes. The OS of SIS = 0, SIS = 1 and SIS = 2 was 28.0 ± 2.9, 16.0 ± 2.8 and 10.0 ± 7.0 months, respectively (p = 0.000). Similar results were also observed for PFS. Multivariate analysis of the model with SIS revealed that the SIS was a significant independent biomarker for predicting OS and PFS. The nomogram showed that the C-index was improved to 0.677 when the SIS factor was incorporated. Furthermore, the 3-year OS rates for patients in the SIS-high group (SIS = 1 and SIS = 2) undergoing concurrent radiotherapy with a single agent (CCRT-1) and concurrent radiotherapy with two agents (CCRT-2) were 42% and 15%, respectively (p = 0.039). The t-ROC curve showed that the SIS was more sensitive than other prognostic factors for predicting overall survival. CONCLUSION: The SIS may be a useful prognostic marker in elderly patients with ESCC receiving radiotherapy alone or chemoradiotherapy. The SIS showed a better predictive ability for OS than the continuous variable Alb and could stratify patient prognosis in different therapeutic regimens. CCRT-1 may be the best treatment for SIS-high patients.

Studies on crystal structures, optical, dyeing and biological properties of protoberberine alkaloids and their supramolecular salts.

The novel Palmatine (PLT)-based supramolecular salt palmatine-sulfosalicylic acid (PLT-SSA) was designed and synthesized, and its structures was determined by the single crystal X-ray diffraction. It is found that PLT-SSA exhibited enhancing thermodynamic stability, fluorescence intensity and emission lifetime in crystal state, which indicated that these structures and aromatic rings may give more overlap between the host-guest units and give rise to a long-lived charge-separated state. In addition, the dyeing properties and toxicity of these protoberberine alkaloid (BBC and PLTCl) and their supramolecular salts will be developed in this work used as yellow dyes for development multifunctional fabrics.

Identified IGSF9 association with prognosis and hypoxia in nasopharyngeal carcinoma by bioinformatics analysis.

BACKGROUND: Despite improvements in nasopharyngeal carcinoma (NPC) treatment, patients with recurrence and metastasis still have a poor prognosis. Thus, the identification of novel biomarkers is urgently needed to predict outcomes and tailor treatment for NPC. METHODS: Four data sets were downloaded from Gene Expression Omnibus, and one data set GSE68799 of which was applied to filtrate key modules and hub genes by construction of a co-expression network. Other data sets (GSE12452 and GSE53819) were used to verify hub genes. The data set GSE102349 was devoted to identify prognostic hub genes by survival analysis. To explored whether prognostic hub genes are related to hypoxia signatures in NPC, correlation analysis was carried out, and followed by functional verification experiments of those genes in vitro. RESULTS: By co-expression network analysis, blue module was regarded as a key module in the benign and malignant group, and IGSF9 of the blue module was identified as a prognostic hub gene. Moreover, IGSF9 is expected to be a innovative hypoxia-related gene in NPC based on the strong associativity between expression of IGSF9 and hypoxia scores of three signatures (99-gene, 26-gene and 15-gene). Further functional studies verified that down-regulated expression of IGSF9 could reduce the proliferation, migration and invasion ability of NPC cells, and hypoxia could induce the expression of IGSF9. CONCLUSION: IGSF9 was identified to be relevant to prognosis and involved in hypoxia in NPC. IGSF9 might serve as one novel prognostic indicator of NPC in the future.

Isoprenylated Phenolic Compounds from Morus macroura as Potent Tyrosinase Inhibitors.

Three new Diels-Alder adducts, macrourins E - G (1: -3: ), one new 2-arylbenzofuran, macrourin H (4: ), and eight known Diels-Alder adducts (5: -12: ) were isolated from Morus macroura. Their structures were elucidated through extensive analysis of spectroscopic data. The 1H NMR and ECD trends in the determination of the configurations of these Diels-Alder adducts were summarized. The tyrosinase inhibitory activities of all compounds isolated were evaluated, and the new compounds (1: -4: ) as well as the eight known compounds (5: -12: ) were found to be potent with IC50 values ranging from 0.39 to 4.54 µM. Among them, 1 showed the best tyrosinase inhibitory activity with an IC50 value of 0.39 µM, approximately 50 times stronger than the positive control, kojic acid.

[Study on quality evaluation of Dihuang (Rehmannia glutinosa) by two-dimension HPLC fingerprints and chemometrics methods].

The study is to establish the two-dimension HPLC fingerprints of Dihuang (Rehmannia glutinosa), by HPLC-PDA and HPLC-ELSD methods. The separations were performed on Waters Atlantis®T3（4.6 mm× 250 mm，5 µm）and Welch Ultimate®Hilic-NH2（4.6 mm× 250 mm，5 µm）columns with the gradient elution of acetonitrile-0.01% phosphoric acid and acetonitrile-water, respectively. The chromatographic display wavelength for PDA detector was set at 203 nm. For HPLC-ELSD, the nebulizer was set as cooling mode, the drift tube temperature was set at 60 °C and the gas pressure was 35.0 psi. Based on similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine, 26 and 10 chromatographic peaks were determined as common components for HPLC-PDA and HPLC-ELSD fingerprints, respectively. Chemometrics analyses, such as similarity analysis; cluster analysis and principal component analysis, were performed on the common peak areas in two-dimension fingerprints for 41 batches of Dihuang from multiple sources. The results showed that the HPLC-PDA fingerprint could distinguish dried rehmannia root between different sources, and HPLC-ELSD fingerprint could differentiate dried rehmannia root from prepared rehmannia root. The two-dimension fingerprints were established with advantages of a good degree of separation, abundant chemical information and multi-components identified including two nucleosides (adenosine and uridine)，four iridoid glycosides (catalpa alcohol，rehmaionoside D，rehmaionoside A and leonuride)，two phenylethanoid glycosides (acteoside and cistanoside A) and nine sugars. The method is simple and practical, which could be used for the identification and quality assessment for Dihuang.

Two new phenolic compounds from the tuber of Sparganium stoloniferum.

Two new phenolic compounds, 2-(2-hydroxyphenyl)-4-methoxycarbonyl-5-hydroxybenzofuran (1) and 1-methoxycarbonyl-2, 3-dihydroxydibenzo[b, f]oxepine (2), were isolated from the tuber of Sparganium stoloniferum. The structures of both new compounds were determined on basis of spectroscopic means including HR-ESI-MS, 1D and 2D NMR experiments.

[Caffeoyl phenylethanoid glycosides from Callicarpa kwangtungensis].

Phytochemical investigation on the EtOH extract from the aerial part of Callicarpa kwangtungensis led to the isolation and characterization of 10 caffeoyl phenylethanoid glycosides, 2'-acetylacteoside (1), tubuloside E (2), acteoside (3), tubuloside B (4), isoacteoside (5), alyssonoside (6), 2'-acetylforsythoside B (7), brandioside (8), forsythoside B (9), and poliumoside (10). Compound 4 was isolated from the plants of Verbenaceae,and 6 was obtained from the Callicarpa genus, for the first time, while compounds 1, 2, 5 and 7 were firstly reported from the plant.

An integrated strategy for quality control of Pseudobulbus Cremastrae seu Pleiones based on Q-marker.

Pseudobulbus Cremastrae seu Pleiones (PCsP), a traditional Chinese medicine known as ‶Shan-Ci-Gu″, possesses properties for clearing heat, counteracting toxicity, dissipating phlegm, and resolving masses. As a TCM with multiple bases, the dried pseudobulbs of Pleione bulbocodioides (PB), Pleione yunnanensis (PY) and Cremastra appendiculata (CA) are considered to be the official sources of PCsP. Additionally, several unofficial substitutes are also available in the market. To enhance the quality control of PCsP, an integrated strategy based on Q-marker was proposed. Initially, a study of integrating plant metabolomics, target isolation, structure identification, and activity testing afforded five Q-markers, including three new compounds. Furthermore, a quality evaluation method using a single standard to determine multi-components (SSDMC) based on Q-marker was established, which could effectively distinguish PB from CA and the counterfeit herbs. Finally, the transitivity of Q-markers was explored through a representative Chinese compound prescription containing PCsP. The results indicated that the identified Q-markers together with the established analysis methods could be effectively applied for quality control of PCsP and its preparations.

Abietane diterpenoids from Caryopteris incana (Thunb.) Miq. And their HIF-2α inhibitory activities in vitro.

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A-K (1-11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7, 9, 15, and 16 showed significant inhibitory effects with IC50 values ranging from 12.73 to 23.80 µM. The preliminary structure-activity relationship of these compounds was also discussed.

Hong Guo Ginseng Guo (HGGG) protects against kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome and regulating intestinal flora.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes which leads to end-stage renal failure and approximately one-third of patients need dialysis. There is still a lack of effective and specific treatment for DN. Searching new drugs from natural foods is an alternative approach to treat diabetes and its complications. Hong Guo Ginseng Guo (HGGG), a berry with palatability and nutritional benefits, has exhibited medicinal properties to mitigate the progression of DN. PURPOSE: This study investigates the effects of HGGG on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats and elucidates the mechanisms underlying its reno-protective and diabetes management benefits. METHODS: The LC-MS spectra method identified the primary ingredients in HGGG. To induce DN, male Sprague-Dawley (SD) rats received a single intraperitoneal injection of 75 mg/kg STZ. Over an eight-week treatment period, we assessed biochemical parameters including blood glucose, urine albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and urine N-acetyl-beta-d-glucosaminidase (NAG). Tissue pathology was examined using Masson's trichrome, Periodic Acid-Schiff (PAS), and Hematoxylin-Eosin (H&E) stains. We analyzed pro-inflammatory mediators and tissue fibrosis extent using Western blotting and immunohistochemistry. Gut microbiota composition was characterized via 16S rDNA sequencing. RESULTS: Seventeen chemical compounds were identified, with lobetyolin, luteolin, and rutin highlighted as the primary active elements. HGGG extract appeared to confer renal protection, demonstrated by improvements in UACR, BUN, and urine NAG levels. The reno protective effects in HGGG-treated DN rats were linked to reduced renal fibrosis and inhibition of the NLRP3 inflammasome. Additionally, HGGG administration improved gut barrier integrity and altered the gut microbiota in DN rats, increasing the relative abundance of beneficial bacteria known for regulating polyamines and producing short-chain fatty acids (SCFAs), including Ruminococcus, Barnesiella_sp, Anaerovoracaceae, and Prevotellaceae_NK3B31. Meanwhile, treatment with HGGG decreasing the presence of Oscillospira, potential pathogens responsible for producing lipopolysaccharide (LPS). CONCLUSION: HGGG has potential as a beneficial fruit for managing diabetes and its associated complications through modulation of the gut microbiota.

Elucidation of the Mechanisms and Molecular Targets of Run-zao-zhiyang Capsule for Itch based on Network Pharmacology, Molecular Docking and In Vitro Experiment.

BACKGROUND: Traditional Chinese medicine formula (TCMF) Run-zao-zhi-yang capsule (RZZY) is commonly used in treating itch in China. However, there are few studies on its mechanisms. In this study, we revealed the mechanisms and molecular targets of RZZY for itch by network pharmacology, molecular docking, and in vitro experiments. METHODS: The network pharmacology consisted of active ingredient collection, target acquisition, enrichment analysis, biological process analysis, and network construction. Molecular docking was carried out using molegro virtual docker (MVD) software. LPS-induced RAW 264.7 cells were used to evaluate the in vitro anti-inflammatory activity. RESULTS: We collected 483 high-confidence targets that interacted with 16 active compounds of RZZY, including 121 common genes related to itch. 43 important targets and 20 important pathways were identified according to the network and system analysis. Target-pathway network function analysis suggested that RZZY is treated for itch by multiple ways in immune regulation, hormone adjustment, anti-inflammation, and anti-oxidation. Molecular docking results demonstrated that daidzein and formononetin could be closely combined with 4 proteins. In vitro experiments displayed that RZZY, sophocarpine, catalpol, emodin, and daidzein had suppressive effects against TNF-α, IL-1ß, or IL-6 production in LPS-induced RAW 264.7 cells. Interestingly, the result of network pharmacology revealed that RZZY might be more suitable for senile pruritus, consistent with the bibliometric analysis of RZZY's clinical indications. CONCLUSION: This study illustrated the potential mechanisms and molecular targets of RZZY for itch, which may contribute to the proper use of RZZY in clinical practice.

Polyacetylenes with xanthine oxidase inhibitory activity from the medicinal and edible fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Five new polyacetylene derivatives (1-5), cyclocodonlandiynosides A-E, and eight known analogues (6-13) were isolated and identified from the fruits of Cyclocodon lancifolius. Their structures were established via spectroscopic and chemical methods, including NMR, HRESIMS, enzymatic hydrolysis, Mo2(OAc)4-induced circular dichroism and sugar derivatization. Compound 1 contains a nitrogenous fragment, which was rarely found in C14 polyacetylenes. Compounds 3 and 4 are polyacetylene glucosides possessing novel aglycones. All the isolated polyacetylenes (except 12) were screened for their xanthine oxidase (XO) inhibitory activity. All the tested compounds, at the concentration of 62.5 µg/mL, showed XO inhibiting effects. Among them, 13 and 3 showed the most potent XO inhibitory activity with IC50 values of 87.65 and 96.32 µM, compared to the positive control allopurinol with an IC50 value of 19.25 µM.

Four new constituents from the fruits of Cyclocodon lancifolius (Roxburgh) Kurz.

Phytochemical analysis of the fruits of Cyclocodon lancifolius led to the isolation of two new phenylpropanoid-derived glycosides (1-2), two new geranyl glucosides (3-4), and nine known compounds (5-13). Their chemical structures were elucidated by extensive spectroscopic data. The absolute configuration of the sugar moiety was determined by hydrolysis and derivatization. All compounds were evaluated for their xanthine oxidase (XO) and α-glucosidase inhibitory activities, and four compounds showed weak inhibitory activity towards XO.

Upregulated Long Non-coding RNA Lnc-MRPL39-2:1 Induces the Growth and Invasion of Nasopharyngeal Carcinoma by Binding to HuR and Stabilizing ß-Catenin mRNA.

Long non-coding RNAs (lncRNAs) have been to regulate tumor progression and therapy resistance through various molecular mechanisms. In this study, we investigated the role of lncRNAs in nasopharyngeal carcinoma (NPC) and the underlying mechanism. Using lncRNA arrays to analyze the lncRNA profiles of the NPC and para-tumor tissues, we detected the novel lnc-MRPL39-2:1, which was validated by in situ hybridization and by the 5' and 3' rapid amplification of the cDNA ends. Further, its role in NPC cell growth and metastasis was verified in vitro and in vivo. The researchers conducted the RNA pull-down assays, mass spectrometry (MS), dual-luciferase reporter assays, RNA immunoprecipitation (RIP) assays, and the MS2-RIP assays were then used to identify the lnc-MRPL39-2:1-interacting proteins and miRNAs. We found that lnc-MRPL39-2:1, which was highly expressed in in NPC tissues, was related to a poor prognosis in NPC patients. Furthermore, lnc-MRPL39-2:1 was shown to induce the growth and invasion of NPC by interacting directly with the Hu-antigen R (HuR) to upregulate ß-catenin expression both in vivo and in vitro. Lnc-MRPL39-2:1 expression was also suppressed by microRNA (miR)-329. Thus, these findings indicate that lnc-MRPL39-2:1 is essential in NPC tumorigenesis and metastasis and highlight its potential as a prognostic marker and therapeutic target for NPC.

Prenylated flavonoids from Morus nigra and their insulin sensitizing activity.

Six undescribed prenylated flavonoids, nigragenons H-M, and four known compounds, were isolated from Morus nigra L. Their structures were elucidated through extensive analysis of spectroscopic data, and their absolute configurations were established by time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. The insulin sensitizing activities of all compounds were investigated using insulin-resistant 3T3-L1 adipocytes. At a high concentration (30 µM), all compounds except nigragenon I enhanced insulin-stimulated glucose uptake in insulin-resistant 3T3-L1 adipocytes. Furthermore, nigragenons J-L and the promoted adiponectin secretion in the model cells. Among them, nigragenon L showed the most potent effect at a low concentration of 10 µM, which was comparable to that of rosiglitazone at a concentration of 1 µM. Furthermore, using the Lantha Screen™ TR-FRET assay, nigragenon L was confirmed to be the ligand of PPARγ, showing potent binding affinity toward PPARγ with an IC50 value of 2.8 µM.

Abietane diterpenoids from Dracocephalum moldavica L. and their anti-inflammatory activities in vitro.

Five undescribed abietane diterpenoids, dracocephalumoids A-E, together with six known analogues were isolated from the aqueous EtOH extract of aerial parts of Dracocephalum moldavica L.. The structures were elucidated through extensive analysis of spectroscopic data, and their absolute configurations were established by Mosher's method and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculation. Cell-based anti-inflammatory assays displayed that dracocephalumoid A, uncinatone, trichotomone F and caryopterisoid C showed potent suppressive effects against TNF-α, IL-1ß or NO production in LPS-induced RAW 264.7 cells, with IC50 values ranging from 1.12 to 5.84 µM. The structure-activity relationship of these compounds was also discussed.

Secondary Nasopharyngeal Mixed Adenoneuroendocrine Carcinoma After Radical Radiotherapy for Nasopharyngeal Carcinoma: A Rare Case and Literature Review.

The incidence of primary mixed adenoneuroendocrine carcinoma (MANEC) is rapidly increasing. MANEC mainly arises from the gastrointestinal tract, but occasionally it occurs as a pathological type of second primary malignancy (SPM). These SPMs can occur in the nasopharynx. Herein we describe the case of a first secondary nasopharyngeal MANEC that was detected 20 years after radical radiotherapy for nasopharyngeal carcinoma. The patient was a 50-year-old man who was admitted to our hospital after experiencing 1 month of left nasal congestion and ipsilateral tinnitus caused by a nasopharyngeal mass that was detected via physical examination and magnetic resonance imaging. A biopsy specimen from this nasopharyngeal lesion led to a histopathological diagnosis of recurrent nasopharyngeal carcinoma. He underwent high-dose palliative radiotherapy, followed by a course of gemcitabine-cisplatin-based adjuvant chemotherapy. These treatments failed to achieve local control of the tumor, and progressive left earache emerged. Another two forceps biopsies of the external auditory canal mass were conducted, and immunohistochemical testing for adenocarcinoma and neuroendocrine carcinoma markers including CK7, CK8, CK18, carcinoembryonic antigen, synaptophysin, chromogranin A, and CD56 was conducted. The diagnosis of MANEC was ultimately confirmed 5 months after the first visit, and one additional cycle of chemotherapy was subsequently performed. The patient died of hepatic metastases 8 months after the final diagnosis. Knowledge of this rare case will raise awareness of MANEC as a new pathological type of SPM originating in the nasopharynx, which will reduce delays and promote early diagnosis.

Phenolic compounds isolated from Morus nigra and their α-glucosidase inhibitory activities.

A novel benzofuranone unprecedentedly with a prenyl group at C-3, nigranol A (1), a new flavonol, nigranol B (2), and three known compounds, sanggenon M (3), nigrasin C (4), and nigrasin A (5) were isolated from the twigs of Morus nigra Linn. Their structures were elucidated on the basis of the analysis of multiple spectroscopic data. All of the compounds, along with eight previously isolated ones (6-13) were investigated for their α-glucosidase inhibitory activities. The result showed that compounds 1-13 except 4 exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 2 and 7 were the best α-glucosidase inhibitory candidates with IC50 values at 1.63 and 1.43 µM, respectively. Furthermore, the structure-activity relationships of the sanggenon-type flavanones were summarized.

Comparison of a Concurrent Fluorouracil-Based Regimen and a Taxane-Based Regimen Combined with Radiotherapy in Elderly Patients with Esophageal Squamous Cell Carcinoma.

Elderly patients with esophageal carcinoma may benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen has not been determined. The aim of our study was to assess the efficiency and tolerance of treatment with a concurrent 5-fluorouracil (5-Fu)-based regimen and a taxane-based regimen combined with radiotherapy in elderly patients with esophageal squamous cell carcinoma (ESCC). A total of 46 patients with ESCC aged older than 65 years were included in this study. The patient population was divided into two treatment groups: 24 patients who received CCRT with a 5-Fu-based regimen were allocated to the PF group, and 22 patients who received CCRT with a taxane-based regimen were allocated to the DP group. The median overall survival (OS), median progression-free survival (PFS), overall response rate, and treatment-related toxicity were assessed. For patients in the PF group, the median OS time was 27.8 ± 9.1 months, and the median PFS time was 12.5 ± 2.7 months. Patients in the DP group had comparable survival outcomes, with a median OS time of 34.4 ± 6.4 months and a median PFS time of 21.1 ± 6.4 months (P = .296 and P = .115, respectively). Grade ≥3 leukocytopenia and grade ≥2 anemia occurred in 63.6% and 59.1% of patients in the DP group, respectively, and in 25.0% and 16.7% of patients in the PF group, respectively. Our results suggest that CCRT with a taxane-based regimen results in a higher incidence of treatment-related toxicity than CCRT with a 5-Fu-based regimen but comparable survival outcomes.

Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells.

Radiotherapy is one of the standard treatments for glioma patients; however, its clinical efficacy is limited by radioresistance. We identified a mechanism of such resistance mediated by linc-RA1 (radioresistance-associated long intergenic noncoding RNA 1). Linc-RA1 was upregulated in radioresistant glioma cells and glioma tissue samples, compared with radiosensitive cells and nontumor tissues. Linc-RA1 was associated with inferior overall survival and advanced clinical stage of glioma. Linc-RA1 promoted glioma radioresistance in vitro and in vivo. Mechanistically, linc-RA1 stabilized the level of H2B K120 monoubiquitination (H2Bub1) by combining with H2B and inhibiting the interaction between H2Bub1 and ubiquitin-specific protease 44 (USP44), which inhibited autophagy, thus contributing to glioma radioresistance. These results reveal that linc-RA1-mediated autophagy is a key mechanism of radioresistance and is an actionable target for improving radiotherapy efficacy in patients with glioma.