Effect of Kangfuxiaomi suppository on pelvic inflammatory disease in rats.

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1ß and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1ß levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway.

Harnessing the Therapeutic Potential of Ginsenoside Rd for Activating SIRT6 in Treating a Mouse Model of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent global condition and a common precursor to liver cancer, yet there is currently no specific medication available for its treatment. Ginseng, renowned for its medicinal and dietary properties, has been utilized in NAFLD management, although the precise underlying mechanism remains elusive. To investigate the effectiveness of ginsenoside Rd, we employed mouse and cell models to induce NAFLD using high-fat diets, oleic acid, and palmitic acid. We explored and confirmed the specific mechanism of ginsenoside Rd-induced hepatic steatosis through experiments involving mice with a liver-specific knockout of SIRT6, a crucial protein involved in metabolic regulation. Our findings revealed that administration of ginsenoside Rd significantly reduced the inflammatory response, reactive oxygen species (ROS) levels, lipid peroxide levels, and mitochondrial stress induced by oleic acid and palmitic acid in primary hepatocytes, thereby mitigating excessive lipid accumulation. Moreover, ginsenoside Rd administration effectively enhanced the mRNA content of key proteins involved in fatty acid oxidation, with a particular emphasis on SIRT6 and its target proteins. We further validated that ginsenoside Rd directly binds to SIRT6, augmenting its deacetylase activity. Notably, we made a significant observation that the protective effect of ginsenoside Rd against hepatic disorders induced by a fatty diet was almost entirely reversed in mice with a liver-specific SIRT6 knockout. Our findings highlight the potential therapeutic impact of Ginsenoside Rd in NAFLD treatment by activating SIRT6. These results warrant further investigation into the development of Ginsenoside Rd as a promising agent for managing this prevalent liver disease.

Antioxidative effect of Periplaneta americana extract on dextran sulfate sodium-induced ulcerative colitis through activation of the Nrf2 signal.

CONTEXT: Periplaneta americana L. (Blattariae) is used as a treatment for ulcerative colitis (UC) in Chinese traditional medicine. OBJECTIVE: To evaluate the antioxidative activity of P. americana whole body ethanol extract (PAE) on UC mice and whether glycine and proline could be used for quality control and identification of active PAE components. MATERIALS AND METHODS: NCM460 cells were pre-incubated in PAE, AA-L, AA-M, and AA-H (low, high and medium doses of proline and glycine), then treated with recombinant human TNF-α. The glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen (ROS) levels were determined. UC mice were fed with water containing 2.5% dextran sulfate sodium (w/v) after pre-treatment with different doses of PAE once a day for 7 days. ELISA was used to detect the concentrations of inflammation-related factors. Colon tissues of mice were used to detect the activity of myeloperoxidase (MPO), GSH, MDA, and SOD. Histological changes were observed using H&E staining. The expression of target proteins was determined by western blotting. RESULTS: In vivo, PAE treatment reduced the DAI score more than in the model group, restoring the weight and colonic length. It also reduced the severity of colitis, and inflammatory and oxidative stress intensity. Additionally, western blotting showed that the Nrf2 pathway was activated by PAE. In vitro PAE significantly alleviated TNF-α-induced cell damage and oxidative stress, which is relevant to the activation of the Nrf2 pathway. CONCLUSIONS: PAE may relieve oxidative stress through the Nrf2 signaling pathway, and proline and glycine may be used as active components of its antioxidative stress activity.

Uterine torsion complicated by severe placental abruption in the second trimester: a case report and literature review.

BACKGROUND: Uterine torsion is a rare obstetric event that can occur during pregnancy and is difficult to diagnose. Its occurrence may lead to serious adverse pregnancy outcomes. CASE INTRODUCTION: The patient was a 33-year-old woman at 30+ 5 weeks' gestation with a singleton pregnancy. The pregnancy course, including fetal growth, and prenatal examinations were regular. Except for a small amount of vaginal bleeding in early pregnancy and treatment with progesterone, there were no prenatal abnormalities, and the patient denied any trauma or sexual history. The patient was admitted to the emergency department with persistent severe pain in the lower abdomen and slight vaginal bleeding during night sleep. Abdominal pain started two hours prior to admission and was accompanied by nausea, vomiting, and dizziness. Examination revealed positive abdominal tenderness, high uterine tone, and no significant intermittent period of uterine contractions, and measurement of the fetal heart rate by means of the nonstress test revealed a rate of 60 beats per minute. Therefore, placental abruption was highly suspected. Subsequently, an emergency cesarean section was performed under general anesthesia. The newborn boy, with Apgar scores of 0-3-4 after birth and weighing 1880 g, was transferred to the neonatal intensive care unit (NICU) and died two days later due to ineffective rescue. After the uterine incision was sutured, the examination revealed that the uterine incision was located on the posterior wall of the uterus, and the uterus was twisted 180° to the right. The diagnosis after cesarean section was 180° uterine torsion to the right, severe placental abruption, and severe neonatal asphyxia. On the fifth day after surgery, the patient recovered and was discharged from the hospital. CONCLUSIONS: Posterior uterine incision cesarean section may be performed in unexpected circumstances and is also feasible as a safe option for resetting if torsion is not complete. Abdominal pain during pregnancy is less likely to be diagnosed as uterine torsion, which often leads to premature birth, fetal asphyxia, placental abruption, and even perinatal death. Therefore, for abdominal pain during pregnancy, obstetricians should consider the possibility of uterine torsion.

Comparison of machine learning models for predicting the risk of breast cancer-related lymphedema in Chinese women.

Objective: Predictive models for the occurrence of cancer symptoms by using machine learning (ML) algorithms could be used to aid clinical decision-making in order to enhance the quality of cancer care. This study aimed to develop and validate a selection of classification models that used ML algorithms to predict the occurrence of breast cancer-related lymphedema (BCRL) among Chinese women. Methods: This was a retrospective cohort study of consecutive cases that had been diagnosed with breast cancer, stages I-IV. Forty-eight variables were grouped into five feature sets. Five classification models with ML algorithms were developed, and the models' performance and the variables' relative importance were assessed accordingly. Results: Of 370 eligible female participants, 91 had BCRL (24.6%). The mean age of this study sample was 49.89 (SD â€‹= â€‹7.45). All participants had had breast cancer surgery, and more than half of them had had a modified radical mastectomy (n â€‹= â€‹206, 55.5%). The mean follow-up time after breast cancer surgery was 28.73 months (SD â€‹= â€‹11.71). Most of the tumors were either stage I (n â€‹= â€‹49, 31.2%) or stage II (n â€‹= â€‹252, 68.1%). More than half of the sample had had postoperative chemotherapy (n â€‹= â€‹227, 61.4%). Overall, the logistic regression model achieved the best performance in terms of accuracy (91.6%), precision (82.1%), and recall (91.4%) for BCRL. Although this study included 48 predicting variables, we found that the five models required only 22 variables to achieve predictive performance. The most important variable was the number of positive lymph nodes, followed in descending order by the BCRL occurring on the same side as the surgery, a history of sentinel lymph node biopsy, a dietary preference for meat and fried food, and an exercise frequency of less than three times per week. These factors were the most influential predictors for enhancing the ML models' performance. Conclusions: This study found that in the ML training dataset, the multilayer perceptron model and the logistic regression model were the best discrimination models for predicting the outcome of BCRL, and the k-nearest neighbors and support vector machine models demonstrated good calibration performance in the ML validation dataset. Future research will need to use large-sample datasets to establish a more robust ML model for predicting BCRL deeply and reliably.

Comparative Proteomic Analysis of Liver Tissues and Serum in db/db Mice.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) affects one-quarter of individuals worldwide. Liver biopsy, as the current reliable method for NAFLD evaluation, causes low patient acceptance because of the nature of invasive sampling. Therefore, sensitive non-invasive serum biomarkers are urgently needed. RESULTS: The serum gene ontology (GO) classification and Kyoto encyclopedia of genes and genomes (KEGG) analysis revealed the DEPs enriched in pathways including JAK-STAT and FoxO. GO analysis indicated that serum DEPs were mainly involved in the cellular process, metabolic process, response to stimulus, and biological regulation. Hepatic proteomic KEGG analysis revealed the DEPs were mainly enriched in the PPAR signaling pathway, retinol metabolism, glycine, serine, and threonine metabolism, fatty acid elongation, biosynthesis of unsaturated fatty acids, glutathione metabolism, and steroid hormone biosynthesis. GO analysis revealed that DEPs predominantly participated in cellular, biological regulation, multicellular organismal, localization, signaling, multi-organism, and immune system processes. Protein-protein interaction (PPI) implied diverse clusters of the DEPs. Besides, the paralleled changes of the common upregulated and downregulated DEPs existed in both the liver and serum were validated in the mRNA expression of NRP1, MUP3, SERPINA1E, ALPL, and ALDOB as observed in our proteomic screening. METHODS: We conducted hepatic and serum proteomic analysis based on the leptin-receptor-deficient mouse (db/db), a well-established diabetic mouse model with overt obesity and NAFLD. The results show differentially expressed proteins (DEPs) in hepatic and serum proteomic analysis. A parallel reaction monitor (PRM) confirmed the authenticity of the selected DEPs. CONCLUSION: These results are supposed to offer sensitive non-invasive serum biomarkers for diabetes and NAFLD.

QSAR study of phenolic compounds and their anti-DPPH radical activity by discriminant analysis.

Phenolic compounds (PCs) could be applied to reduce reactive oxygen species (ROS) levels, and are used to prevent and treat diseases related to oxidative stress. QSAR study was applied to elucidate the relationship between the molecular descriptors and physicochemical properties of polyphenol analogues and their DPPH radical scavenging capability, to guide the design and discovery of highly-potent antioxidant substances more efficiently. PubMed database was used to collect 99 PCs with antioxidant activity, whereas, 105 negative PCs were found in ChEMBL database; their molecular descriptors were generated with Python's Rdkit package. While the molecular descriptors significantly related to the antioxidant activity of PCs were filtered by t-test. The prediction QSAR model was then established by discriminant analysis, and the obtained model was verified by the back-substitution and Leave-One-Out cross-validation methods along with heat map. It was revealed that the anti-DPPH radical activity of PCs was correlated with the drug-likeness and molecular fingerprints, physicochemical, topological, constitutional and electronic property. The established QSAR model could explicitly predict the antioxidant activity of polyphenols, thus were applicable to evaluate the potential of candidates as antioxidants.

Toxin diversity revealed by de novo transcriptome assembly for venom gland in two species of spiders (Trichonephila clavata and Sinopoda pengi).

During long-term predator-prey coevolution, spiders have generated a vast diversity of toxins. Trichonephila clavata is a web-spinning spider whose large, well-constructed webs and venomous arsenal facilitate prey capture. In contrast, Sinopoda pengi is an ambush predator with agile locomotion and strong chelicerae for hunting. In this study, transcriptomic analysis was performed to describe the predicted toxins of S. pengi and T. clavata. A total of 43 and 47 of these unigenes from S. pengi and T. clavata, respectively, were predicted to have toxin activity. Putative neurotoxins were classified to the family level according to cysteine arrangement; 4 and 6 toxin families were produced by S. pengi and T. clavata, respectively. In addition, potential metalloproteases, acetylcholinesterases, serine proteases, hyaluronidases and phospholipases were found by annotation in databases. In summary, molecular templates with potential application value for medical and biological fields were obtained by classifying and characterizing presumed venom components, which established a foundation for further study of venom.

Periplaneta americana extract ameliorates dextran sulfate sodium-induced ulcerative colitis via immunoregulatory and PI3K/AKT/NF-κB signaling pathways.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) with a low cure rate. Periplaneta americana is a traditional American Cockroach and reportedly has potential therapeutic roles for UC treatment; however, its mechanisms remain unclear. To address this, we investigated the therapeutic effects and underlying molecular mechanisms of Ento-A, a Periplaneta americana extract, in a dextran sulfate sodium (DSS)-induced chronic and recurrent UC mouse model. Ento-A treatment decreased pro-inflammatory cytokine secretion, disease activity index (DAI), colon mucosa damage index (CMDI), histopathological scores (HS), and increased colon length. Additionally, Ento-A effectively increased interleukin-4 (IL-4), and forkhead transcription factor protein 3 (Foxp3) expression levels, while it abated interferon-γ (IFN-γ) and IL-17 levels in spleen lymphocytes. Conversely, in mesenteric lymph nodes, IL-4 and Foxp3 expression were decreased, while IFN-γ and IL-17 expression was increased. Furthermore, Ento-A blocked p-PI3K, p-AKT,*and p-NF-κB activation. In conclusion, Ento-A improved UC symptoms and exerted therapeutic effects by regulating immune responses and inhibiting PI3K/AKT/NF-κB signaling.

Differential DNA methylation and changing cell-type proportions as fibrotic stage progresses in NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is characterized by changes in cell composition that occur throughout disease pathogenesis, which includes the development of fibrosis in a subset of patients. DNA methylation (DNAm) is a plausible mechanism underlying these shifts, considering that DNAm profiles differ across tissues and cell types, and DNAm may play a role in cell-type differentiation. Previous work investigating the relationship between DNAm and fibrosis in NAFLD has been limited by sample size and the number of CpG sites interrogated. RESULTS: Here, we performed an epigenome-wide analysis using Infinium MethylationEPIC array data from 325 individuals with NAFLD, including 119 with severe fibrosis and 206 with no histological evidence of fibrosis. After adjustment for latent confounders, we identified 7 CpG sites whose DNAm associated with fibrosis (p < 5.96 × 10-8). Analysis of RNA-seq data collected from a subset of individuals (N = 56) revealed that gene expression at 288 genes associated with DNAm at one or more of the 7 fibrosis-related CpGs. DNAm-based estimates of cell-type proportions showed that estimated proportions of natural killer cells increased, while epithelial cell proportions decreased with disease stage. Finally, we used an elastic net regression model to assess DNAm as a biomarker of fibrotic stage and found that our model predicted fibrosis with a sensitivity of 0.93 and provided information beyond a model based solely on cell-type proportions. CONCLUSION: These findings are consistent with DNAm as a mechanism underpinning or marking fibrosis-related shifts in cell composition and demonstrate the potential of DNAm as a possible biomarker of NAFLD fibrosis.

The zinc finger transcription factor, KLF2, protects against COVID-19 associated endothelial dysfunction.

Coronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its patho-mechanism being incompletely understood. Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. The objective of the present study is to evaluate whether kruppel-like factor 2 (KLF2), a master regulator of vascular homeostasis, represents a therapeutic target for COVID-19-induced endothelial dysfunction. Here, we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1ß and TNF-α, two cytokines elevated in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Pharmacologic (atorvastatin and tannic acid) and genetic (adenoviral overexpression) approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis, and reduced angiogenesis). Finally, knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion. Collectively, the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.

Periplaneta americana extract promotes intestinal mucosa repair of ulcerative colitis in rat

Abstract Purpose: To investigate the mechanism of Periplaneta americana extract promoting intestinal mucosal repair of OXZ-induced colitis in rat. Methods: All experiments used an equal number of male and female SD rats (n=48). We injected OXZ into the colon to induce UC rat model. To determine the optimal concentration of P. Americana's extract (PA-40), it was classified into low (L), medium (M), and high (H) doses. After OXZ treatment, each drug was administered by enema for 7 consecutive days. Rats were divided into the following 6 groups: (1) Saline treatment group (NC), (2) OXZ treatment UC model group (MC), (3) OXZ + budesonide group (BUN), (4) OXZ + PA-40 L group, (5) OXZ + PA-40 M group, (6) OXZ + PA-40 H group. Disease activity index (DAI) scores, colon length, histopathological score, serum cytokine level (IL-4, IL-10, iNOS, tNOS), and amount of MPO, EGF, IL-13 in colonic mucosa were measured. Results: PA treatment had a significant healing effect on the OXZ-colitis model and significantly reduced the lesioned area, especially in the PA-40H groups. PA treatment did not alter the expression of IL-10 and MPO level, but increased EGF (epidermal growth factor) and decrease IL-13 in the colonic tissue. PA inhibited the rise of NOSs (nitric oxide synthase) and decreased the serum IL-4 level. Conclusions: The data suggest that Periplaneta americana extract may be a potential compound for the treatment of colonic lesions. The mechanism may be related to inhibiting the secretion of IL-13 and promoting the formation of EGF.

Beneficial effect of compound essential oil inhalation on central fatigue.

BACKGROUNDS: Although the physical and mental enhancement effect of essential oils have been proved, the beneficial effect of essential oil in central fatigue remains unclear. In this study, we extracted essential oils from nine aromatic plants to make a compound essential oil, and detected the therapeutic effect of central fatigue by daily aerial diffusion. METHODS: Thirty-three rats were randomly and equally divided into control group, chronic sleep deprivation group, and compound essential oil inhalation group. Central fatigue was generated by chronic sleep deprivation. RESULTS: After 21-day various interferences, it is found that the sleep deprivation rats showed an evident decrease in physical endurance, negative emotion, and cognitive dysfunction compared with the control group, and the group that treated with the compound essential oil behaved significantly better than central fatigue group. CONCLUSION: We concluded that this formula of essential oils could alleviate central fatigue on rats, and our study provides a new direction of application of aromatic therapy, which could be expanded to insomnia, depression and other healthy issue in the further research.

Cytotoxicity of the Defensive Secretion from the Medicinal Insect Blaps rynchopetera.

Blaps rynchopetera Fairmaire has long been used as a folk medicine by the Yi and Bai ethnic groups in China to treat fever, cough, gastritis, boils, and tumors. In the present study, the cytotoxicity of the defensive secretion (TDS) of B. rynchopetera against AGS Caco-2, HepG2 U251 and Bel-7402 was tested, and the results revealed that TDS had potent cytotoxicity against testing cells with IC50 values of 45.8, 17.4, 53.6, 98.4 and 23.4 µg/mL, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis was employed to clarify the cytotoxic constituents in TDS of B. rynchopetera and five volatile compounds, including 2-ethyl-2,5-cyclohexadiene-1,4-dione (3, 31.00%), 1-tridecene (5, 28.02%), 2-methyl-2,5-cyclohexadiene-1,4-dione (2, 22.86%), hydroquinone (4, 1.33%), and p-benzoquinone (1, 1.01%), were identified. Chemical constituent investigation on TDS further supported the presence of 5 above compounds. A cytotoxic assay indicated that compounds 1, 2, 3 and 4 exhibited significant cytotoxicity against the testing cell lines, implying that benzoquinones and hydroquinone played important roles in the cytotoxicity of TDS of B. rynchopetera. TDS is a cytotoxic natural material and further studies investigating mechanisms and inhibitory activities on other cell lines is warranted.

Five New Phenolic Compounds with Antioxidant Activities from the Medicinal Insect Blaps rynchopetera.

Five new phenolic compounds rynchopeterines A-E (1-5), in addition to thirteen known phenolics, were isolated from Blaps rynchopetera Fairmaire, a kind of medicinal insect utilized by the Yi Nationality in Yunnan Province of China. Their structures were established on the basis of extensive spectroscopic analyses (1D and 2D NMR, HR-MS, IR) along with calculated electronic circular dichroism method. Rynchopeterines A-E (1-4) exhibited significant antioxidant activities with IC50 values of 7.67-12.3 µg/mL measured by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Besides, rynchopeterines B (2) and C (3) showed mild cytotoxicity against tumor cell Caco-2 and A549.

[Detection and clinical significance of PML protein expression of acute promyelocytic leukemia cells].

Objective To study the expression patterns of promyelocytic leukemia (PML) protein at different stages of acute promyelocytic leukemia (APL) and investigate the effects that the arsenical, all-trans retinoic acid (ATRA) and chemotherapeutic drugs on PML protein expression patterns. Methods The bone marrow cells of 42 APL patients, NB4 cells and MR2 cells were collected and treated separately with 1 µmol/L arsenic trioxide (As2O3), 1 µmol/L tetra-arsenic tetra-sulfide (As4S4), 1 µmol/L ATRA, 10 mg/L cytosine arabinoside, and 1 mg/L homoharringtonine. The changes of fluorescent signals before and after the treatment were detected by indirect immunofluorescence technique. Results The 87.5% of initial onset APL cases showed small fluorescent signals (fluorescent signals in the nucleus look like a starry sky, more than 30 fluorescent light dots per cell); 91.67% of complete remission APL cases manifested large fluorescent signals (fluorescent signals in the nucleus are larger, fewer than 30 fluorescent light dots per cell); and 83.33% of relapse APL cases presented small fluorescent signals. Compared with control group without medication, the PML protein expression of APL cells in initial onset cases had larger fluorescent signals in the ATRA group, As2O3 group and As4S4 group, whereas there were no significant changes in the arabinoside cytosine group and the homoharringtonine group. In addition, ATRA transformed the PML protein expression of NB4 cells from small fluorescent signals into large ones, but did not change small fluorescent signals of the PML protein expression in MR2 cells. Also, As2O3 and As4S4 turned the PML protein expression of NB4 and MR2 cells from small fluorescent signals into large ones. Conclusion Detection of PML protein expression patterns of APL cells has practical application values for evaluating the prognosis of APL and making a rational choice of drugs.

Diagnose human colonic tissues by terahertz near-field imaging.

Based on a terahertz (THz) pipe-based near-field imaging system, we demonstrate the capability of THz imaging to diagnose freshly surgically excised human colonic tissues. Through THz near-field scanning the absorbance of the colonic tissues, the acquired images can clearly distinguish cancerous tissues from healthy tissues fast and automatically without pathological hematoxylin and eosin stain diagnosis. A statistical study on 58 specimens (20 healthy tissues and 38 tissues with tumor) from 31 patients (mean age: 59 years; range: 46 to 79 years) shows that the corresponding diagnostic sensitivity and specificity on colonic tissues are both 100%. Due to its capability to perform quantitative analysis, our study indicates the potential of the THz pipe-based near-field imaging for future automation on human tumor pathological examinations.

Roscovitine suppresses CD4+ T cells and T cell-mediated experimental uveitis.

BACKGROUND: T cells are essential for the development of uveitis and other autoimmune diseases. After initial activation, CD4+ lymphocytes express the co-stimulatory molecule OX40 that plays an important role in T cell proliferation. Cyclin dependent kinase 2 (CdK2) plays a pivotal role in the cell cycle transition from G1 to S phase. In addition, recent research has implicated CdK2 in T cell activation. Thus, we sought to test the immunosuppressive effect of roscovitine, a potent CdK2 inhibitor, on CD4+ T cell activation, proliferation, and function. DESIGN AND METHODS: Mouse CD4+ T cells were activated by anti-CD3 and anti-CD28 antibodies. The expression of OX40, CD44, and CdK2 were analyzed by flow cytometry. In addition, cell cycle progression and apoptosis of control and roscovitine-treated T lymphocytes were measured by BrdU incorporation and annexin V assay, respectively. Furthermore, the immunoregulatory effect of roscovitine was evaluated in both ovalbumin-induced uveitis and experimental autoimmune uveitis (EAU) models. RESULTS: In this study, we found that T cell activation induced OX40 expression. Cell cycle analysis showed that more CD4+OX40+ cells entered S phase than OX40- T cells. Concurrently, CD4+OX40+ cells had a higher level of CdK2 expression. Roscovitine treatment blocked activated CD4+ cells from entering S phase. In addition, roscovitine not only reduced the viability of CD4+ lymphocytes but also suppressed T cell activation and cytokine production. Finally, roscovitine significantly attenuated the severity of T cell-dependent, OX40-enhanced uveitis. CONCLUSION: These results implicate CdK2 in OX40-augmented T cell response and expansion. Furthermore, this study suggests that roscovitine is a novel, promising, therapeutic agent for treating T cell-mediated diseases such as uveitis.

Heterosynaptic long-term depression mediated by ATP released from astrocytes.

Heterosynaptic long-term depression (hLTD) at untetanized synapses accompanying the induction of long-term potentiation (LTP) spatially sharpens the activity-induced synaptic potentiation; however, the underlying mechanism remains unclear. We found that hLTD in the hippocampal CA1 region is caused by stimulation-induced ATP release from astrocytes that suppresses transmitter release from untetanized synaptic terminals via activation of P2Y receptors. Selective stimulation of astrocytes expressing channelrhodopsin-2, a light-gated cation channel permeable to Ca(2+) , resulted in LTD of synapses on neighboring neurons. This synaptic modification required Ca(2+) elevation in astrocytes and activation of P2Y receptors, but not N-methyl-D-aspartate receptors. Furthermore, blocking P2Y receptors or buffering astrocyte intracellular Ca(2+) at a low level prevented hLTD without affecting LTP induced by SC stimulation. Thus, astrocyte activation is both necessary and sufficient for mediating hLTD accompanying LTP induction, strongly supporting the notion that astrocytes actively participate in activity-dependent synaptic plasticity of neural circuits.