First-line surgery versus first-line assisted reproductive technology for women with deep infiltrating endometriosis: a systematic review and meta-analysis.

Background: The efficiency of different first-line treatments, such as first-line surgery and assisted reproductive technology (ART), in women with deep infiltrating endometriosis (DIE) is still unclear due to a lack of direct comparative trials. This systematic review and meta-analysis aim to elucidate and compare the efficacies of first-line treatments in patients with DIE, with an emphasis on fertility outcomes. Methods: An exhaustive search of PubMed Central, SCOPUS, EMBASE, MEDLINE, Cochrane trial registry, Google Scholar, and Clinicaltrials.gov databases was done to identify studies directly comparing first-line surgery and assisted reproductive technology (ART) for DIE, and reporting fertility-related outcomes. Pooled estimates for each of the binary outcomes were reported as odds ratios (ORs) with 95% confidence intervals (CIs). The results were pooled using a random-effects model with the Mantel-Haenszel technique. Results: Our results show that pregnancy rate per patient (OR, 1.47; 95% CI, 0.59 to 3.63), pregnancy rate per cycle (OR, 1.16; 95% CI, 0.45 to 2.99), and live births per patient (OR, 1.66; 95% CI, 0.56 to 4.91) were comparable in DIE patients, treated with surgery or ART as a first line of treatment. When both complete and incomplete surgical DIE excision procedures were taken into account, surgery was associated with a significant enhancement in the pregnancy rate per patient (OR, 1.63; 95% CI, 1.11 to 2.40). Conclusion: The available evidence suggests that both first-line surgery and ART can be effective DIE treatments with similar fertility outcomes. However, further analysis reveals that excluding studies involving endometriomas significantly alters the understanding of treatment efficacy between surgery and ART for DIE-associated infertility. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=426061, identifier CRD42023426061.

Clinical phenotype of a Kallmann syndrome patient with IL17RD and CPEB4 variants.

Background: This study aimed to characterize the clinical phenotype and genetic variations in patients with Kallmann syndrome (KS). Methods: This study involved the collection and analysis of clinical data from an individual with sporadic KS. Following this, peripheral blood samples were obtained from the patient and his parents. Genomic deoxyribonucleic acid was extracted and subjected to whole-exome sequencing and genomic copy number variation (CNV) detection. Finally, Sanger sequencing was performed to validate the suspected pathogenic variants. Results: Whole-exome sequencing confirmed that the child carried both the IL17RD variant (c.2101G>A, p.Gly701Ser) inherited from the mother and the new CPEB4 variant (c.1414C>T, p.Arg472*). No pathogenic CNVs were identified in CNV testing. Conclusion: Bioinformatics analysis shows that the IL17RD protein undergoing Gly701Ser mutation and is speculated to be phosphorylated and modified, thereby disrupting fibroblast growth factor signaling. This study also suggested that the CPEB4 might play a crucial role in the key signaling process affecting olfactory bulb morphogenesis. Overall, the findings of this study broaden the gene expression profile of KS-related pathogenic genes. This offers a new avenue for exploring the pathogenic mechanism of KS and provides valuable insights for precise clinical diagnosis and treatment strategies for this condition.

Amide proton transfer imaging has added value for predicting extraprostatic extension in prostate cancer patients.

Background: Prostate cancer invades the capsule is a key factor in selecting appropriate treatment methods. Accurate preoperative prediction of extraprostatic extension (EPE) can help achieve precise selection of treatment plans. Purpose: The aim of this study is to verify the diagnostic efficacy of tumor size, length of capsular contact (LCC), apparent diffusion coefficient (ADC), and Amide proton transfer (APT) value in predicting EPE. Additionally, the study aims to investigate the potential additional value of APT for predicting EPE. Method: This study include 47 tumor organ confined patients (age, 64.16 ± 9.18) and 50 EPE patients (age, 61.51 ± 8.82). The difference of tumor size, LCC, ADC and APT value between groups were compared. Binary logistic regression was used to screen the EPE predictors. The receiver operator characteristic curve analysis was performed to assess the diagnostic performance of variables for predicting EPE. The diagnostic efficacy of combined models (model I: ADC+LCC+tumor size; model II: APT+LCC+tumor size; and model III: APT +ADC+LCC+tumor size) were also analyzed. Results: APT, ADC, tumor size and the LCC were independent predictors of EPE. The area under the curve (AUC) of APT, ADC, tumor size and the LCC were 0.752, 0.665, 0.700 and 0.756, respectively. The AUC of model I, model II, and model III were 0.803, 0.845 and 0.869, respectively. The cutoff value of APT, ADC, tumor size and the LCC were 3.65%, 0.97×10-3mm2/s, 17.30mm and 10.78mm, respectively. The sensitivity/specificity of APT, ADC, tumor size and the LCC were 76%/89.4.0%, 80%/59.6%, 54%/78.9%, 72%/66%, respectively. The sensitivity/specificity of model I, Model II and Model III were 74%/72.3%, 82%/72.5% and 84%/80.9%, respectively. Data conclusion: Amide proton transfer imaging has added value for predicting EPE. The combination model of APT balanced the sensitivity and specificity.

[Retracted] Activation of the LKB1­SIK1 signaling pathway inhibits the TGF­ß­mediated epithelial­mesenchymal transition and apoptosis resistance of ovarian carcinoma cells.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion and migration assay data shown in Figs. 2C and 3F were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes, which had either already been published or were under consideration for publication at around the same time. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 2837­2844, 2018; DOI: 10.3892/mmr.2017.8229].

Anti-oxidative, anti-apoptotic, and anti-inflammatory activities of Connarus semidecandrus Jack ethanol extract in UVB-irradiated human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. AIM OF THE STUDY: Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). MATERIALS AND METHODS: Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of -20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography-mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. RESULTS: Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. CONCLUSIONS: Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products.

[Clinical and genetic analysis of a child with early-onset severe obesity].

OBJECTIVE: To explore the clinical phenotype and genetic etiology of a child with early-onset severe obesity. METHODS: A child who presented at the Department of Endocrinology, Hangzhou Children's Hospital on August 5, 2020 was selected as the study subject. Clinical data of the child were reviewed. Genomic DNA was extracted from peripheral blood samples of the child and her parents. Whole exome sequencing (WES) was carried out on the child. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. RESULTS: This child was a 2-year-and-9-month girl featuring severe obesity with hyperpigmentation on the neck and armpit skin. WES revealed that she has harbored compound heterozygous variants of the MC4R gene, namely c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp). Sanger sequencing confirmed that they were respectively inherited from her father and mother. The c.831T>A (p.Cys277*) has been recorded by the ClinVar database. Its carrier frequency among normal East Asians was 0.000 4 according to the 1000 Genomes, ExAC, and gnomAD databases. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as pathogenic. The c.184A>G (p.Asn62Asp) has not been recorded in the ClinVar, 1000 Genomes, ExAC and gnomAD databases. Prediction using IFT and PolyPhen-2 online software suggested it to be deleterious. Based on the guidelines from the ACMG, it was determined as likely pathogenic. CONCLUSION: The c.831T>A (p.Cys277*) and c.184A>G (p.Asn62Asp) compound heterozygous variants of the MC4R gene probably underlay the early-onset severe obesity in this child. Above finding has further expanded the spectrum of MC4R gene variants and provided a reference for the diagnosis and genetic counseling for this family.

Physiological Functions of FBW7 in Metabolism.

FBW7 is the recognition subunit of the SCF (Skp1-Cullin1-F-box proteins) E3 ubiquitin ligase complex, and it determines the specificity of the SCF substrate. SCFFBW7 is a recognized tumor suppressor because of its ability to degrade many proto-oncogenic substrates. Recent studies have shown that FBW7 plays a key role in metabolism by targeting the degradation of critical regulators involved in cellular metabolism in a ubiquitin-dependent manner. Here, we review recent studies, which highlight the important role of FBW7 in metabolism.

Hymenocallis littoralis ameliorates inflammatory responses in LPS-stimulated RAW264.7 cells and HCl/EtOH-induced gastric mucosal injury via targeting the MAPK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hymenocallis littoralis (Jacq.) Salisb. Also known as Pancratium littorale Jacq. And Hymenocallis panamensis Lindl., is a medicinal plant from the family Amarylideceae used for emetic and wound healing and has manifested anti-neoplastic, anti-oxidant, and anti-viral properties. AIM OF THE STUDY: The aim of this paper is to investigate the anti-inflammatory potential and molecular mechanism of H. littoralis against lipopolysaccharide (LPS)-induced macrophages and in vivo HCl/EtOH-induced gastritis mucosal injury models. MATERIALS AND METHODS: The production of pro-inflammatory cytokines and mediators was evaluated by Griess assay, RT-PCR, and real-time PCR. Moreover, the relevant proteins of mitogen-activated protein kinases (MAPKs) including ERK, JNK, p38, c-Jun, and c-Fos were detected using immunoblotting. RESULTS: We demonstrated that H. littoralis prominently dampened production of nitric oxide (NO) in LPS-, poly I:C-, or pam3CSK-stimulated RAW264.7 cells; down-regulated the expression levels of interleukin 6 (IL-6) and inducible nitric oxide synthase; and markedly attenuated the luciferase activities of AP-1 reporter promoters. Moreover, H. littoralis administration prominently downregulated c-Fos and c-Jun phosphorylation as well as JNK1, ERK2, and MKK7 overexpression in HEK 293T cells. Furthermore, H. littoralis displayed anti-inflammatory effects in the HCl/EtOH-induced gastritis mice model. CONCLUSIONS: Cumulatively, these results demonstrated that H. littoralis exerts eminently anti-inflammatory activities in LPS-stimulated RAW264.7 cells in vitro and in HCl/EtOH-induced gastritis mice models in vivo. These activities could be attributed to its modulatory effects on the MAPK signaling pathway.

Characterization of ginsenoside compound K loaded ionically cross-linked carboxymethyl chitosan-calcium nanoparticles and its cytotoxic potential against prostate cancer cells.

BACKGROUD: Ginsenoside compound K (GK) is a major metabolite of protopanaxadiol-type ginsenosides and has remarkable anticancer activities in vitro and in vivo. This work used an ionic cross-linking method to entrap GK within O-carboxymethyl chitosan (OCMC) nanoparticles (Nps) to form GK-loaded OCMC Nps (GK-OCMC Nps), which enhance the aqueous solubility and stability of GK. METHODS: The GK-OCMC Nps were characterized using several physicochemical techniques, including x-ray diffraction, transmission electron microscopy, zeta potential analysis, and particle size analysis via dynamic light scattering. GK was released from GK-OCMC Nps and was conducted using the dialysis bag diffusion method. The effects of GK and GK-OCMC Nps on PC3 cell viability were measured by using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Fluorescent technology based on Cy5.5-labeled probes was used to explore the cellular uptake of GK-OCMC Nps. RESULTS: The GK-OCMC NPs had a suitable particle size and zeta potential; they were spherical with good dispersion. In vitro drug release from GK-OCMC NPs was pH dependent. Moreover, the in vitro cytotoxicity study and cellular uptake assays indicated that the GK-OCMC Nps significantly enhanced the cytotoxicity and cellular uptake of GK toward the PC3 cells. GK-OCMC Nps also significantly promoted the activities of both caspase-3 and caspase-9. CONCLUSION: GK-OCMC Nps are potential nanocarriers for delivering hydrophobic drugs, thereby enhancing water solubility and permeability and improving the antiproliferative effects of GK.

Clinicopathological characteristics of primary peritoneal epithelioid mesothelioma of clear cell type: A case report.

RATIONALE: Primary peritoneal epithelioid mesothelioma of clear cell type is an extremely rare entity composed of clear cytoplasm. It is challenging to diagnose because of the morphological resemblance to clear cell tumor. PATIENTS CONCERNS: A 69-year-old male patient had swollen lymph nodes in the right inguinal region for 7 months and was constipated for 1 month. DIAGNOSIS: The patient was diagnosed as peritoneal epithelioid mesothelioma of clear cell type based on computed tomography scan, pathology, immunohistochemistry, special staining and whole-exome sequencing. This patient harbored VHL gene alteration in exon 1 and homologous recombination defect (with a score of 45). This finding indicated that this patient might be sensitive to platinum-based therapy and Poly ADP-ribose Polymerase (PARP) inhibitor. This patient carried no microsatellite instability, a low level of tumor mutation burden, and a high extent of intratumoral heterogeneity. Eighteen neoantigens were detected. INTERVENTIONS: The patient received surgery-based multidisciplinary treatment by integrating cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC was administered with docetaxel 120 mg plus cisplatin 120 mg, at 43°C, for 60 minutes. After operation, the patient received intravenous (IV) chemotherapy with docetaxel 60 mg, pemetrexed 750 mg and cisplatin 100 mg, and then intraperitoneal (IP) chemotherapy with docetaxel 40 mg. The patient received interventional therapy of hepatic artery embolization for 5 times. OUTCOMES: Regular follow-up was performed until Oct 14, 2020. The patient died 31.6 months later owing to incomplete intestinal obstruction. LESSONS: Primary peritoneal epithelioid mesothelioma of clear cell type needs to be differentiated from a variety of clear cell tumors. This disease is characterized by specific genetic alteration. Whole-exome sequencing contributes to guide individualized therapy. CRS-HIPEC helps achieve long-term overall survival.

Euodia pasteuriana Methanol Extract Exerts Anti-Inflammatory Effects by Targeting TAK1 in the AP-1 Signaling Pathway.

Euodia pasteuriana A. Chev. ex Guillaumin, also known as Melicope accedens (Blume) T.G. Hartley, is a herbal medicinal plant native to Vietnam. Although Euodia pasteuriana is used as a traditional medicine to treat a variety of inflammatory diseases, the pharmacological mechanisms related to this plant are unclear. This study aimed to investigate the anti-inflammatory effects of a methanol extract of Euodia pasteuriana leaves (Ep-ME) on the production of inflammatory mediators, the mRNA expression of proinflammatory genes, and inflammatory signaling activities in macrophage cell lines. The results showed that Ep-ME strongly suppressed the release of nitric oxide (NO) in RAW264.7 cells induced with lipopolysaccharide (LPS), pam3CysSerLys4 (Pam3CSK), and polyinosinic-polycytidylic acid (poly I:C) without cytotoxicity. A reverse transcription-polymerase chain reaction further confirmed that Ep-ME suppressed the expression of interleukin 6 (IL-6), matrix metalloproteinase-1 (MMP1), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-3 (MMP3), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP9) at the transcriptional level and reduced the luciferase activities of activator protein 1 (AP-1) reporter promoters. In addition, immunoblotting analyses of the whole lysate and nuclear fraction, as well as overexpression assays demonstrated that Ep-ME decreased the translocation of c-Jun and suppressed the activation of transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 signaling pathways. These results imply that Ep-ME could be developed as an anti-inflammatory agent that targets TAK1 in the AP-1 signaling pathway.

Tabebuia impetiginosa: A Comprehensive Review on Traditional Uses, Phytochemistry, and Immunopharmacological Properties.

Tabebuia impetiginosa, a plant native to the Amazon rainforest and other parts of Latin America, is traditionally used for treating fever, malaria, bacterial and fungal infections, and skin diseases. Additionally, several categories of phytochemicals and extracts isolated from T. impetiginosa have been studied via various models and displayed pharmacological activities. This review aims to uncover and summarize the research concerning T. impetiginosa, particularly its traditional uses, phytochemistry, and immunopharmacological activity, as well as to provide guidance for future research. A comprehensive search of the published literature was conducted to locate original publications pertaining to T. impetiginosa up to June 2020. The main inquiry used the following keywords in various combinations in titles and abstracts: T. impetiginosa, Taheebo, traditional uses, phytochemistry, immunopharmacological, anti-inflammatory activity. Immunopharmacological activity described in this paper includes its anti-inflammatory, anti-allergic, anti-autoimmune, and anti-cancer properties. Particularly, T. impetiginosa has a strong effect on anti-inflammatory activity. This paper also describes the target pathway underlying how T. impetiginosa inhibits the inflammatory response. The need for further investigation to identify other pharmacological activities as well as the exact target proteins of T. impetiginosa was also highlighted. T. impetiginosa may provide a new strategy for prevention and treatment of many immunological disorders that foster extensive research to identify potential anti-inflammatory and immunomodulatory compounds and fractions as well as to explore the underlying mechanisms of this herb. Further scientific evidence is required for clinical trials on its immunopharmacological effects and safety.

[Analysis of Genomic Landscape in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the gene mutation occurved in AML patients with 29 kinds of fusion genes and 51 kinds of tumor gene. METHODS: Next-generation sequencing (NGS) was used to detected the 49 kinds of targeted gene. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutation were detected by DNA-based PCR and Sanger sequencing. Twenty-nine kinds of fusion genes were dected by multiplex nested RT-PCR. RESULTS: The total gene mutation rate was 91% (109/121) in all the 121 patients. On average, 2.1 mutated genes per patient were identified, among these 121 patients, coexistence of ≥ 3 mutations was frequent (34.7%). The most commonly mutated genes were NRAS (23.96%, n=29), followed by NPM1 (14.04%, n=17), CEBPA double mutations (14.04%, n=17), KRAS (11.57%, n=14)，FLT3-ITD (10.74%, n=13), CSF3R (10.74%, n=13), TET2 (9.92%, n=12) and IDH1 (9.1%, n=11). Overall, fusion genes were detected in 47 (37.3%) patients, including AML/ETO (n=12), CBFß/MYH11 (n=11), PML/RARa (n=12), MLL rearranagement realated mutation MLL-X (n=10). TLS/ERG (n=1) and DEK/CAN (n=1) in an order of decreasing frequency. Patients with normal karyotype (NK)- AML exhibited more mutations in CEBPA, NPM1, TET2, RUNX1 and IDH1, comparing with abnormal karyotype patients. KRAS mutation in abnormal kayotype patients was significantly higher than that in normal kayotype patients (P=0.014). TP53 mutations were predominantly associated with complex cytogenetics (P=0.199). KRAS mutations were more frequent in core binding factor (CBF) acute myeloid leukemia (AML) and 11q23/MLL rearrangement leukemia, compared with NK-AML (P=0.006 and 0.003, respectively). KIT mutations predominated in CBF-AML (P=0.006). JAK2V617F mutations were detected in two patients and co-occurred with AML-ETO fusions. CONCLUSION: At least one mutation is observed in more than 90% patients. On average, more than 2 mutated genes per patient are identified. Some gene mutations are associated with gene rearrangement.

Micelles modified with a chitosan-derived homing peptide for targeted intracellular delivery of ginsenoside compound K to liver cancer cells.

Ginsenoside compound K (CK), a major metabolite of protopanaxadiol ginsenosides, exhibits significant anticancer activities against various cancer cells. However, CK has poor water solubility and low bioavailability, which have limited its application. In this study, A54 peptide was utilized to fabricate CK-loaded micelles (APD-CK) for liver targeting, using deoxycholic acid-O-carboxymethyl chitosan as the vehicle. The average particle size of APD-CK micelles was about 171.4 nm by dynamic light scattering in the hydrated state and their morphology were spherical with good dispersion. An in vitro release assay indicated pH-responsive and sustained release behavior through a mechanism of non-Fickian diffusion. Moreover, the in vitro cytotoxicity of the APD-CK micelles against HepG2 and Huh-7 cells was significantly stronger than that of CK up to 20 µg/mL. Enhanced cellular uptake of micelles in both cell types was established using confocal fluorescence scanning microscopy and flow cytometry. In addition, western blot analysis revealed that APD-CK micelles could promote the protein expression levels of caspase-3, caspase-9, and poly (ADP-ribose) polymerase. Therefore, APD-CK micelles are a potential vehicle for delivering hydrophobic drugs in liver cancer therapy, enhancing drug targeting and anticancer activity.

Transcriptome Analyses of the Anti-Proliferative Effects of 20(S)-Ginsenoside Rh2 on HepG2 Cells.

20(S)-ginsenoside Rh2 (Rh2), a well-known protopanaxadiol-type ginsenoside from Panax ginseng has especially gained attention for its anticancer activities on various types of human cancer cells. However, the molecular mechanism through which Rh2 promotes apoptosis in hepatocellular carcinoma (HePG2) cells is not known at the transcriptome level. Rh2 can specifically inhibit the proliferation of HePG2 in a dose- and time-dependent manner. Moreover, Rh2 can significantly increase the apoptosis which was related with an increase in protein expression levels of caspase-3, caspase-6, and poly (ADP-ribose) polymerase. Comparison of RNA-seq transcriptome profiles from control group and Rh2-treated group yielded a list of 2116 genes whose expression was significantly affected, which includes 971 up-regulated genes and 1145 down-regulated genes. The differentially expressed genes in p53 signaling pathway and DNA replication may have closely relationships to the cells apoptosis caused by Rh2 treatment. The results of qPCR validation showed that dynamic changes in mRNA, such as CDKN1A, CCND2, PMAIP1, GTSE1, and TP73.

Xinjiang herbal tea exerts immunomodulatory activity via TLR2/4-mediated MAPK signaling pathways in RAW264.7 cells and prevents cyclophosphamide-induced immunosuppression in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: A multi-herb Chinese medicinal formula consisting of a variety of medicinal and edible materials has long been consumed as a hot drink and immune enhancer for its efficiency to increase disease resistance in Xinjiang, China. However, no fundamental data has been collected associated with traditional consumption. The present work was designed to evaluate the immunostimulatory role of Xinjiang herbal tea (XMT-WE) in RAW 264.7 macrophages and cyclophosphamide (CTX)-induced immunosuppression mice model. MATERIALS AND METHODS: RAW 264.7 cells were treated with various concentrations of XMT-WE. Nitric oxide (NO) levels were determined using Griess reagents, and pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α were investigated with a cytometric bead array kit. The effects on mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α were investigated. Furthermore, activation of nuclear factor (NF)-κB and AP-1 mitogen-activated protein kinase (MAPK) signaling pathways was investigated. RESULTS: Pre-treatment with XMT-WE significantly increased secretion of NO, IL-6, and TNF-α. In addition, XMT-WE markedly increased expression of iNOS, COX-2, and TNF-α as well as AP-1 and NF-κB translocation from the cytoplasm into the nucleus, which was associated with an increase of phosphorylated ERK, JNK, and p38 as well as membrane receptors such as toll-like receptor (TLR) 2 and TLR4. Moreover, XMT-WE promoted the secretion of interleukin-2 (IL-2) and interferon-γ (IFN-γ) in cyclophosphamide (CTX)-induced immunosuppressive mice. CONCLUSION: These results indicated that XMT-WE at 50 µg/ml exerts immunomodulatory activity via TLR2/4-mediated MAPK signaling pathways in RAW 264.7 cells. Furthermore, in vivo experiments revealed that XMT-WE at the dose of 50 and 100 mg/kg strongly stimulated inflammatory cytokines.

Senkyunolide H protects against MPP+-induced apoptosis via the ROS-mediated mitogen-activated protein kinase pathway in PC12 cells.

Senkyunolide H (SNH) is a phthalide isolated from the rhizome of Ligusticum chuanxiong Hort. that has been reported to have several pharmacological activities, including anti-atherosclerotic, antiproliferative, and cytoprotective effects. In this study, we investigated the neuroprotective effects and potential mechanisms of SNH against 1-methyl-4-phenylpyridinium (MPP+)-induced oxidative stress. We demonstrated that SNH pretreatment significantly attenuated MPP+-induced neurotoxicity and apoptosis in PC12 cells. In addition, SNH attenuated the effect of MPP+ on the expression of the pro-apoptotic factors Bax and caspase-3. Meanwhile, SNH prevented oxidative stress by reducing reactive oxygen species generation, mitochondrial membrane potential loss, cytochrome C release, and malondialdehyde levels while increasing antioxidant enzyme activity (e.g., superoxide dismutase, catalase, and glutathione peroxidase). In addition, SNH inhibited nuclear accumulation of nuclear factor-κB and c-Jun N-terminal kinase and phosphorylation p38 mitogen-activated protein kinases (MAPKs). Overall, this investigation provides novel evidence that SNH exerts neuroprotective effects via the ROS-mediated MAPK pathway and represents a potential preventive or therapeutic agent for neuronal disorders.

Ozone detoxification of patulin in aqueous solution and cytotoxic evaluation using human hepatic carcinoma cells.

Patulin often contaminates fruits and fruit-base products, which seriously threats the health of consumers. In this study, ozone was used to degrade patulin in aqueous solution, and investigated the cytotoxicity of patulin after ozone detoxification on human hepatic carcinoma cells (HepG2) using MTT assay and apoptosis assay. Patulin was rapidly degraded from 24.59 mg/L to 9.85 mg/L within 180 s by 10.60 mg/L of ozone at a flow rate of 90 mL/min, and reduced by 59.94%. The half maximal inhibitory concentration (IC50) of patulin on HepG2 cells was 9.32 µmol/L after 24 h of exposure, and it showed a dose dependent effect. After 90 s of ozone detoxification, the cell viability of HepG2 cells obviously increased from 42.31% to 93.96%, and the total apoptotic cells significantly reduced from 22.24% to 11.18% after 180 s of ozone treatment. The results clearly show the great potential of ozone in degrading patulin in liquid foods.

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling.

BACKGROUND/AIMS: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC. METHODS: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice. RESULTS: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development. CONCLUSION: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.