Antitumor Effect of Poplar Propolis on Human Cutaneous Squamous Cell Carcinoma A431 Cells.

Propolis is a gelatinous substance processed by western worker bees from the resin of plant buds and mixed with the secretions of the maxillary glands and beeswax. Propolis has extensive biological activities and antitumor effects. There have been few reports about the antitumor effect of propolis against human cutaneous squamous cell carcinoma (CSCC) A431 cells and its potential mechanism. CCK-8 assays, label-free proteomics, RT-PCR, and a xenograft tumor model were employed to explore this possibility. The results showed that the inhibition rate of A431 cell proliferation by the ethanol extract of propolis (EEP) was dose-dependent, with an IC50 of 39.17 µg/mL. There were 193 differentially expressed proteins in the EEP group compared with the control group (p < 0.05), of which 103 proteins (53.37%) were upregulated, and 90 proteins (46.63%) were downregulated. The main three activated and suppressed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were extracellular matrix (ECM)-receptor interaction, amoebiasis, cell adhesion molecules (CAMs), nonalcoholic fatty liver disease (NAFLD), retrograde endocannabinoid signaling, and Alzheimer's disease. The tumor volume of the 100 mg/kg EEP group was significantly different from that of the control group (p < 0.05). These results provide a theoretical basis for the potential treatment of human CSCC A431 cell tumors using propolis.

Beyond traditional light: NIR-II light-activated photosensitizers for cancer therapy.

With increasing demand for the accurate and safe treatment of cancer, non-invasive photodynamic therapy (PDT) has received widespread attention. However, most conventional photosensitizers are typically excited by short-wavelength visible light (400-700 nm), thus substantially hindering the penetration of light and the therapeutic effectiveness of the PDT procedure. Fortunately, near-infrared (NIR) light (>700 nm), in particular, light in the second near-infrared region (NIR-II, 1000-1700 nm) has a higher upper radiation limit, greater tissue tolerance, and deeper tissue penetration compared with traditional short-wavelength light excitation, and shows considerable potential in the clinical treatment of cancer. Therefore, it is of paramount importance and clinical value to develop photosensitizers that are excited by NIR-II light. In this review, for the first time we focus completely on recent progress made with various NIR-II photosensitizers for cancer treatment via PDT, and we briefly present the ongoing challenges and prospects of currently developed NIR-II photosensitizers for clinical practice in the near future. We believe that the above topics will inspire broad interest in researchers from interdisciplinary fields that include chemistry, materials science, pharmaceuticals, and clinical medicine, and provide insightful perspectives for exploiting new NIR-II photosensitizers for biomedical applications.

External treatment of traditional Chinese medicine for functional dyspepsia in children: Protocol for a systematic review and network meta-analysis.

BACKGROUND: Functional dyspepsia (FD) is a common digestive system disease in pediatrics, usually affects normal growth and increases health care expenditure. Many investigations have demonstrated that external treatment of traditional Chinese medicine (TCM) has certain advantages in the treatment of FD children, but the effectiveness, safety, and advantages of various methods have not been confirmed by high-quality meta-analyses. This study will conduct a systematic review and network meta-analysis to evaluate the differences and effectiveness in external treatments of TCM, in order to provide a reference for further clinical treatment for FD in children. METHODS: Nine electronic databases, including PubMed, Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, Wan-Fang Database and one clinical trial register platforms: ClinicalTrials.gov (www.ClinicalTrials.gov/) will be searched using English and Chinese search strategies. All eligible studies are randomized controlled trials of TCM external treatment for FD in children, published on or before July 20, 2022. The screening process will be developed by 2 independent authors, and network meta-analysis will be performed with RevMan (V5.3) software. RESULTS: This study will provide a high-quality synthesis to assess the effectiveness and safety on the external treatment of TCM for children with FD. CONCLUSION: The results of this study will provide evidence to judge whether the external treatment of TCM are effective interventions for children with FD. ETHICS AND DISSEMINATION: The results of this meta-analysis and meta-regression will be disseminated through publication in a peer-reviewed journal and presented at a relevant conference. The information used in the network meta-analysis does not contain individual patient data. Therefore, ethical approval was not required. PROSPERO REGISTRATION NUMBER: CRD42022360429.

Modified citrus pectin prevents isoproterenol-induced cardiac hypertrophy associated with p38 signalling and TLR4/JAK/STAT3 pathway.

Modified citrus pectin (MCP) is a specific inhibitor of galectin-3 (Gal-3) that is regarded as a new biomarker of cardiac hypertrophy, but its effect is unclear. The aim of this study is to investigate the role and mechanism of MCP in isoproterenol (ISO)-induced cardiac hypertrophy. Rats were injected with ISO to induce cardiac hypertrophy and treated with MCP. Cardiac function was detected by ECG and echocardiography. Pathomorphological changes were evaluated by the haematoxylin eosin (H&E) and wheat germ agglutinin (WGA) staining. The hypertrophy-related genes for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß-myosin heavy chain (ß-MHC), and the associated signal molecules were analysed by qRT-PCR and western blotting. The results show that MCP prevented cardiac hypertrophy and ameliorated cardiac dysfunction and structural disorder. MCP also decreased the levels of ANP, BNP, and ß-MHC and inhibited the expression of Gal-3 and Toll-like receptor 4 (TLR4). Additionally, MCP blocked the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), but it promoted the phosphorylation of p38. Thus, MCP prevented ISO-induced cardiac hypertrophy by activating p38 signalling and inhibiting the Gal-3/TLR4/JAK2/STAT3 pathway.

Gentianella acuta prevents acute myocardial infarction induced by isoproterenol in rats via inhibition of galectin-3/TLR4/MyD88/NF-кB inflammatory signalling.

Gentianella acuta (G. acuta), as a folk medicine, was used to treat heart disease by the Ewenki people in Inner Mongolia. However, the effect of G. acuta on acute myocardial infarction (AMI) is not clear. To explore the mechanisms of G. acuta on isoproterenol (ISO)-induced AMI, rats were administered G. acuta for 28 days, then injected intraperitoneally with ISO (85 mg/kg) on days 29 and 30. An electrocardiogram helped to evaluate the myocardial injury. Serum lactate dehydrogenase (LDH), creatinine kinase (CK) and aspartate aminotransferase (AST) levels were evaluated, and haematoxylin eosin, Masson's trichrome staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining were used to detect myocardial histological changes. Radioimmunoassay was used to measure serum tumour necrosis factor alpha (TNFα) and interleukin (IL)-6. An enzyme-linked immunosorbent assay kit was used to analyse serum galectin-3 (Gal-3) levels. Immunohistochemistry, Western blotting and reverse transcription polymerase chain reaction were used to examine relevant molecular events. The results revealed that pre-treatment with G. acuta decreased the elevation in the ST segment; reduced serum LDH, CK and AST levels; alleviated cardiac structure disorder; and reduced inflammatory infiltration, abnormal collagen deposition and cardiomyocyte apoptosis that were induced by ISO. Furthermore, pre-treatment with G. acuta inhibited serum Gal-3 levels and Gal-3 expression in heart tissue, and also impeded TLR4/MyD88/NF-кB signalling activation, which ultimately prevented the expression of inflammatory cytokines. The study indicated that pre-treatment with G. acuta protects against ISO-induced AMI, and the protective role may be related to inhibiting Gal-3/TLR4/MyD88/NF-кB inflammatory signalling.

Modified citrus pectin ameliorates myocardial fibrosis and inflammation via suppressing galectin-3 and TLR4/MyD88/NF-κB signaling pathway.

Myocardial fibrosis (MF) plays a key role in the development and progression of heart failure (HF) with limited effective therapies. Galectin-3 (Gal-3) is a biomarker associated with fibrosis and inflammation in patients with HF. The Gal-3 inhibitor modified citrus pectin (MCP) protects against cardiac dysfunction, though the underlying mechanism remains unclear. The aim of this study was to investigate the effect and mechanism of MCP on MF using an isoproterenol (ISO)-induced rat model of HF. Cardiac function was analyzed by echocardiography and electrocardiography. Histopathological changes in the heart tissue were assessed by hematoxylin-eosin and Masson trichrome staining. The mRNA and protein expression levels of signaling molecules and pro-inflammatory cytokines were monitored by immunohistochemistry, western blot, qRT-PCR and ELISA analyses. The results demonstrated that MCP ameliorated cardiac dysfunction, decreased myocardial injury and reduced collagen deposition. Furthermore, MCP downregulated the expression of Gal-3, TLR4 and MyD88, thereby inhibiting NF-κB-p65 activation. MCP also decreased the expression of IL-1ß, IL-18 and TNF-α, which have been implicated in the pathogenesis of HF. These inhibitory effects were observed on day 15 and continued until day 22. Taken together, these results suggest that MCP ameliorates cardiac dysfunction through inhibiting inflammation and MF. These effects may be through downregulating Gal-3 expression and suppressing activation of the TLR4/MyD88/NF-κB signaling pathway. The present study supports the use of Gal-3 as a therapeutic target for the treatment of MF after myocardial infarction.

[Electroacupuncture improved learning-memory ability by reducing hippocampal apoptosis and suppressing JNK signaling in rats with vascular dementia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation on the expression of c-Jun terminal kinase(JNK)signaling pathway-related proteins in the hippocampus of vascular dementia (VD) rats, so as to explore its mechanisms underlying improvement of VD. METHODS: Male Sprague-Dawley rats were randomly divided into sham operation, model and EA groups (n＝10 rats per group). The VD model was prepared by repeated occlusion of the bilateral common carotid arteries for 10 min and reperfusion for 10 min (3 times in total). The rats in the EA group received EA (2 Hz, 2 mA) at "Dazhui"(GV14)，"Baihui"(GV20), and bilateral "Housanli"(ST36) ，"Geshu"(BL17) for 10 min, once daily for 14 days. The learning-memory abi-lity was detected by Morris water maze tests, the distribution of hippocampal neurons detected by Nissl staining, and the apoptosis of hippocampal neurons detected by using TdT-mediated dUTP nick-end labeling (TUNEL) method. The expressions of JNK, phosphorylated JNK (p-JNK), cysteine-containing aspartate-specific proteases-8 (Caspase-8) and Caspase-3 proteins were detected by Western blot. RESULTS: After modeling and compared with the sham operation group, the escape latency was significantly prolonged (P<0.01) and the number of safe-platform quadrant crossing obviously decreased (P<0.01), suggesting a reduction of learning-memory ability. The number of hippocampal neurons was considerably reduced (P<0.01), and that of hippocampal apoptotic neurons remarkably increased in the model group (P<0.01). Whereas, the expression levels of hippocampal apoptosis-related proteins as JNK, p-JNK, Caspase-8 and Caspase-3, as well as the apoptotic index were significantly up-regulated (P<0.01). Following EA intervention, the learning-memory ability was apparently improved (P<0.01), and the number of hippocampal neurons was considerably increased (P<0.01), the hippocampal apoptotic cell number, apoptosis index and the expression levels of JNK, p-JNK, Caspase-8 and Caspase-3 were significantly down-regulated (P<0.01). CONCLUSION: EA intervention can improve the learning-memory ability of VD rats, which may be associated with its effects in reducing hippocampal apoptosis by suppressing JNK signaling pathway.

The aqueous extract of Gentianella acuta improves isoproterenol­induced myocardial fibrosis via inhibition of the TGF­ß1/Smads signaling pathway.

Gentianella acuta (G. acuta) is one of the most commonly used herbs in Chinese Mongolian medicine for the treatment of heart disease. Previously, it was found that G. acuta ameliorated cardiac function and inhibited isoproterenol (ISO)­induced myocardial fibrosis in rats. In this study, the underlying anti­fibrotic mechanism of G. acuta was further elucidated. Histopathological changes in the heart were observed by hematoxylin­eosin, Masson trichrome and wheat germ agglutinin staining. Relevant molecular events were investigated using immunohistochemistry and western blotting. The results revealed that G. acuta caused improvements in myocardial injury and fibrosis. G. acuta also inhibited collagens I and III and α­smooth muscle actin production in heart tissue. G. acuta downregulated the expression of transforming growth factor ß1 (TGF­ß1) and notably inhibited the levels of phosphorylation of TGF­ß receptors I and II. Furthermore, G. acuta caused downregulation of the intracellular mothers against decapentaplegic homolog (Smads)2 and 4 expression and inhibited Smads2 and 3 phosphorylation. The results further demonstrated that the mechanism underlying anti­myocardial fibrosis effects of G. acuta was based upon the suppression of the TGF­ß1/Smads signaling pathway. Therefore, G. acuta may be a potential therapeutic agent for ameliorating myocardial fibrosis.

The antitumor natural product tanshinone IIA inhibits protein kinase C and acts synergistically with 17-AAG.

Tanshinone IIA (Tan IIA), the primary bioactive compound derived from the traditional Chinese medicine (TCM) Salvia miltiorrhiza Bunge, has been reported to possess antitumor activity. However, its antitumor mechanisms are not fully understood. To resolve the potential antitumor mechanism(s) of Tan IIA, its gene expression profiles from our database was analyzed by connectivity map (CMAP) and the CMAP-based mechanistic predictions were confirmed/validated in further studies. Specifically, Tan IIA inhibited total protein kinase C (PKC) activity and selectively suppressed the expression of cytosolic and plasma membrane PKC isoforms ζ and ε. The Ras/MAPK pathway that is closely regulated by the PKC signaling is also inhibited by Tan IIA. While Tan IIA did not inhibit heat shock protein 90 (Hsp90), it synergistically enhanced the antitumor efficacy of the Hsp90 inhibitors 17-AAG and ganetespib in human breast cancer MCF-7 cells. In addition, Tan IIA significantly inhibited PI3K/Akt/mTOR signaling, and induced both cell cycle arrest and autophagy. Collectively, these studies provide new insights into the molecular mechanisms responsible for antitumor activity of Tan IIA.

Antioxidant capacity and major polyphenol composition of teas as affected by geographical location, plantation elevation and leaf grade.

Tea polyphenols have been a topic of discussion due to their health benefits. Nevertheless, detailed studies on the antioxidant capacity and polyphenol contents of teas in relation to factors including geographical locations, plantation elevations and leaf grades have been limited. In this study, 53 tea samples were analysed to determine the individual and total catechin and theaflavin contents by HPLC and the total antioxidant capacity by Oxygen Radical Absorbance Capacity (ORAC) methods. Results show that the polyphenol (catechins and theaflavins) contents were significantly influenced by plantation location. Black tea from low plantation elevation contained 22-28% more polyphenols than those from high elevation. Small tea leaves had up to 15% more polyphenols than larger leaves from similar elevation. The results were further confirmed by Principal Composition Analysis (PCA), which grouped the black and green tea samples into 3 different clusters, respectively.

Three new lignanosides from the aerial parts of Lespedeza cuneata.

Three new lignanosides (+)-(8S,7'S,8'S)-burselignan-9'-O-ß-d-glucopyrano side (1), (+)-(8R,7'S,8'R)-isolariciresinol-9'-O-ß-d-fucopyranoside (2), (-)-(8S, 7'R,8'R)-methoxyisoariciresinol-9'-O-α-l-rhamnoside (3), along with four known compounds, were isolated from the aerial parts of Lespedeza cuneata (Dum.Cours.) G.Don. The fucopyranoside has not been reported in this genus previously. Their structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with known analogues in the literature. Compounds 2 and 6 showed moderate hepatoprotective activities.

[Effects of nitrogen additions on soil hydrolase and oxidase activities in Pinus elliottii plantations.] / æ°®æ·»åŠ å¯¹æ¹¿åœ°æ¾æž—åœŸå£¤æ°´è§£é ¶å’Œæ°§åŒ–é ¶æ´»æ€§çš„å½±å“.

We evaluated responses of hydrolase and oxidase activities in a subtropical Pinus elliottii plantation through a nitrogen (N) addition field experiment (dosage level: 0, 40, 120 kg N·hm-2·a-1). The results showed that N additions significantly decreased the carbon, nitrogen and phosphorus related hydrolase and oxidase activities. The activities of ß-1,4-glucosidase (BG), cellobiohydrolase (CBH), ß-1,4-N-acetylglucosaminidase (NAG) and peroxidase (PER) activities were decreased by 16.5%-51.1% due to N additions, and the decrease was more remarkable in the higher N addition treatment. The activities of α-1,4-glucosidase (aG), ß-1,4-xylosidase (BX), acid phosphatase (AP) and phenol oxidase (PPO) were decreased by 14.5%-38.6% by N additions, however, there was no significant difference among the different N addition treatments. Soil enzyme activities varied obviously in different seasons. The activities of BG, NAG, BX, CBH, AP and PPO were in the order of March > June > October, and aG and PER activities were in the order of October > March > June. Most of the soil hydrolase and oxidase activities were positively correlated with soil pH, but negatively with NO3--N content. It indicated that N additions inhibited soil hydrolase and oxidase activities by reducing soil pH and increasing soil nitrification. N additions inhibited the soil organic matter mineralization and turnover in the subtropical area, and the effects were obvious with the increasing dosage of N additions.

[Influence of Electroacupuncture Intervention on Glutamic Acid and Ca2+ Contents and Expression of NMDA Receptor Protein in Hippocampus in Vascular Dementia Rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) intervention on hippocampal glutamate (Glu) and Ca2+ contents, and expression of Glu-N-methyl-D-aspartic acid receptor(NMDAR) and the learning-memory ability in vascular dementia (VD) rats, so as to reveal its mechanisms underlying improvement of VD. METHODS: SD rats were rando-mized into sham operation (sham) group (n=9), model group (n=11) and EA groups (n=10). The VD model was established by repeated bilateral common carotid arteries occlusion and reperfusion plus intraperitoneal injection of sodium nitroprusside. EA (2 Hz, 2 mA) was applied to "Baihui" (GV 20)-"Housanli" (ST 36) and "Geshu" (BL 17)-"Dazhui" (GV 14) for 10 min, once a day for 15 consecutive days. The neurological function was assessed by using stroke index (0-10 points) and neurological deficit scaling(0-10 points). The learning-memory ability was evaluated by using step-down tests. The contents of Glu and Ca2+ in the right hippocampal tissue were determined by using aspectrophotometer and the expression of NMDAR protein in the right hippocampus was detected by immunoblotting. RESULTS: Compared with the sham group, the stroke index and neurological deficit scores, and the reaction latency and the error times of step-down tests, as well as the contents of Glu and Ca2+ and the expression level of NMDAR in the right hippocampus were significantly increased in the model group (P<0.05, P<0.01), while the step-through latency was considerably decreased (P<0.01), suggesting a neurological disorder and a cognitive decline. After EA intervention, the reaction latency and error times of step-down tests, the contents of Glu and Ca2+ and the expression level of NMDAR in the right hippocampus were significantly down-regulated, and the step-through latency was notably increased in comparison with the model group (P<0.01). CONCLUSIONS: EA intervention is able to improve the cognitive ability of VD rats, which may be associated with its effects in reducing the excitatory neurotoxicity of hippocampal Glu-NMDAR and lowering cellular Ca2+ load to resist neuronal injury.

Report: Analysis on pathogen distribution and drug-resistance of incision infection caused by vascular operation.

To investigate pathogen distribution and drug resistance of incision infection caused by vascular operation to reduce postoperative incision infection, this paper retrospectively reviewed and analyzed 635 in-hospital patients taking vascular operation during Jan. 2008 and Dec. 2012. Analyzed data were statistically processed by SPSS 13.0 software, which resulted in 16 infected cases with 2.52% infection rate. A total of 27 pathogens wasisolated from specimens submitted for inspection, including 17 strains of Gram positive bacteria (62.96%) and 10 Gram negative bacteria (37.04%). Besides high sensitivity to imipenem, all bacteria were able to resist antibacterial drugs. Incision infection is proved in this research to be reduced effectively by some means, like complication correction before operation and reasonable application of antibacterial drugs after operation. While during an operation, it is necessary to operate strictly in a bacterium-free environment and wash incisions thoroughly.

[Effect of electroacupuncture intervention at different time-points of post-modeling on hippocampal monoamine neurotransmitter levels in mice with vascular dementia].

OBJECTIVE: To observe the effect of electrocupuncture (EA) intervention at different time-points of post-modeling on behavior and hippocampal monoamine neurotransmitter noradrenalin (NE), dopamine (DA) and 5-hydroxytrypamine (5-HT) contents in vascular dementia (VD) mice, so as to study its mechanism underlying improvement of VD. METHODS: A total of 60 Kunming mice were randomized into sham-operation control (n = 20), VD model (n = 20), EA-day (D)-1 (EA treatment was given from the 1st day on after modeling, n = 10), EA-D-3 (EA was given from the 3rd day on after modeling, n = 10) groups. VD model was established by occlusion of the bilateral cervical common arteries and reperfusion. EA (2 Hz/80 Hz) was applied to "Baihui" (GV 20), "Dazhui" (GV 14),"Zusanli" (ST 36) and "Geshu"(BL 17) for 10 min, once daily for 15 days. Hippocampal NE, DA and 5-HT contents were assayed by fluorospectrophotometry. The mouse's learning-memory ability was assessed by step-down tests. RESULTS: In comparison with the sham-operation control group, the learning-memory ability (marked increase of reaction time and error times, decrease of step-down latency) was apparently lowered in the model group (P < 0.01). The hippocampal NE, DA and 5-HT contents were significantly lower in the model group than in the sham-operation group (P < 0.01). Compared with the model group, the mice's learning-memory ability (marked decrease of reaction time and error times, increase of step-down latency) was significantly increased in EA intervention groups (P < 0.01), and hippocampal NE, DA and 5-HT levels were significantly increased (P < 0.01), and the effect of EA-D-3 group was obviously better than that of the EA-D-1 group (P < 0.05, P < 0.01). CONCLUSION: EA can improve the VD mice's learning-memory ability, which is closely related to its effects in up-regulating hippocampal NE, DA and 5-HT contents, and the effect of later EA intervention after modeling is better.

Analysis of prescription database extracted from standard textbooks of traditional Dai medicine.

BACKGROUND: Traditional Dai Medicine (TDM) is one of the four major ethnomedicine of China. In 2007 a group of experts produced a set of seven Dai medical textbooks on this subject. The first two were selected as the main data source to analyse well recognized prescriptions. OBJECTIVE: To quantify patterns of prescriptions, common ingredients, indications and usages of TDM. METHODS: A relational database linking the prescriptions, ingredients, herb names, indications, and usages was set up. Frequency of pattern of combination and common ingredients were tabulated. RESULTS: A total of 200 prescriptions and 402 herbs were compiled. Prescriptions based on "wind" disorders, a detoxification theory that most commonly deals with symptoms of digestive system diseases, accounted for over one third of all prescriptions. The major methods of preparations mostly used roots and whole herbs. CONCLUSION: The information extracted from the relational database may be useful for understanding symptomatic treatments. Antidote and detoxification theory deserves further research.

[Studies on chemical constituents in bark of Larix olgensis var. koreana].

OBJECTIVE: To study the chemical constituents in bark of Larix olgensis var. koreana. METHOD: The compounds were isolated with silica gel column chromatography and their structures were elucidated on the basis of spectral analysis (IR, EI-MS, 1H-NMR, 13C-NMR). RESULT: Eight compounds were isolated and identified as isopimaric acid (I), beta-sitosterol (II), 24R,5alpha-stigmast-3,6-dione (III), larixol (IV), ferulic acid (V), lariciresinol (VI), secroisolariciresinol (VII) and isolariciresinol (VIII). CONCLUSION: All the compounds were isolated from this plant for the first time.