Effects of aluminum (Al) stress on the isoprenoid metabolism of two Citrus species differing in Al-tolerance.

Isoprenoid metabolism and its derivatives took part in photosynthesis, growth regulation, signal transduction, and plant defense to biotic and abiotic stresses. However, how aluminum (Al) stress affects the isoprenoid metabolism and whether isoprenoid metabolism plays a vital role in the Citrus plants in coping with Al stress remain unclear. In this study, we reported that Al-treatment-induced alternation in the volatilization rate of monoterpenes (α-pinene, ß-pinene, limonene, α-terpinene, γ-terpinene and 3-carene) and isoprene were different between Citrus sinensis (Al-tolerant) and C. grandis (Al-sensitive) leaves. The Al-induced decrease of CO2 assimilation, maximum quantum yield of primary PSII photochemistry (Fv/Fm), the lower contents of glucose and starch, and the lowered activities of enzymes involved in the mevalonic acid (MVA) pathway and 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway might account for the different volatilization rate of isoprenoids. Furthermore, the altered transcript levels of genes related to isoprenoid precursors and/or derivatives metabolism, such as geranyl diphosphate (GPP) synthase (GPPS) in GPP biosynthesis, geranylgeranyl diphosphate synthase (GGPPS), chlorophyll synthase (CHS) and GGPP reductase (GGPPR) in chlorophyll biosynthesis, limonene synthase (LS) and α-pinene synthase (APS) in limonene and α-pinene synthesis, respectively, might be responsible for the different contents of corresponding products in C. grandis and C. sinensis. Our data suggested that isoprenoid metabolism was involved in Al tolerance response in Citrus, and the alternation of some branches of isoprenoid metabolism could confer different Al-tolerance to Citrus species.

IL-6/STAT3 axis is hijacked by GCRV to facilitate viral replication via suppressing type â IFN signaling.

Grass carp reovirus (GCRV) infections and hemorrhagic disease (GCHD) outbreaks are typically seasonally periodic and temperature-dependent, yet the molecular mechanism remains unclear. Herein, we depicted that temperature-dependent IL-6/STAT3 axis was exploited by GCRV to facilitate viral replication via suppressing type Ⅰ IFN signaling. Combined multi-omics analysis and qPCR identified IL-6, STAT3, and IRF3 as potential effector molecules mediating GCRV infection. Deploying GCRV challenge at 18 °C and 28 °C as models of resistant and permissive infections and switched to the corresponding temperatures as temperature stress models, we illustrated that IL-6 and STAT3 expression, genome level of GCRV, and phosphorylation of STAT3 were temperature dependent and regulated by temperature stress. Further research revealed that activating IL-6/STAT3 axis enhanced GCRV replication and suppressed the expression of IFNs, whereas blocking the axis impaired viral replication. Mechanistically, grass carp STAT3 inhibited IRF3 nuclear translocation via interacting with it, thus down-regulating IFNs expression, restraining transcriptional activation of the IFN promoter, and facilitating GCRV replication. Overall, our work sheds light on an immune evasion mechanism whereby GCRV facilitates viral replication by hijacking IL-6/STAT3 axis to down-regulate IFNs expression, thus providing a valuable reference for targeted prevention and therapy of GCRV.

Traditional Chinese medicine for smoking cessation: An umbrella review of systematic reviews and meta-analysis of randomized controlled trials.

INTRODUCTION: Traditional Chinese medicine (TCM) may have special advantages in facilitating smoking cessation, but consensus on effectiveness is lacking. We aim to comprehensively review, update, and refine current evidence on TCM effectiveness and safety. METHODS: Nine databases were searched from their inception up to 28 February 2023. Systematic reviews (SRs) and meta-analysis of TCM for smoking cessation were identified and retrieved. Additional databases and hand searches of RCTs from included SRs were performed for data pooling. Cochrane ROB tools and AMSTAR-2 were used to evaluate the methodological quality of RCTs and SRs, respectively. RCT data are presented as relative risks (RR) or mean differences (MD) with 95% confidence intervals (CI) using RevMan 5.4. RESULTS: Thirteen SRs involving 265 studies with 33081 participants were included. Among these 265 studies, 157 were duplicates (58.36%) and 52 were non-RCTs (19.62%). Combined with the remaining 56 RCTs identified through hand searches, 88 RCTs involving 12434 participants were finally included for data synthesis. All the SRs focused on acupoint stimulation, and the majority were of low or very low quality. The methodological quality of RCTs was either unclear or high risk. For continuous abstinence rate, TCM external interventions were better than placebo in 6 months to 1 year (RR=1.60; 95% CI: 1.14-2.25; I2=27%; n=5533 participants). Compared with placebo, TCM external application was effective in reducing nicotine withdrawal symptoms, and the effect was gradually stable and obvious in the fourth week (MD= -4.46; 95% CI: -5.43 - -3.49; n=165 participants). Twelve RCTs reported adverse events as outcome indicators for safety evaluation, and no serious adverse events occurred. CONCLUSIONS: Despite the methodological limitations of the original studies, our review suggests that TCM intervention shows potential effectiveness on the continuous abstinence rate. Extending the intervention time can enhance the effect of TCM on nicotine withdrawal symptoms. Referred to adverse events, more data for safety evaluation are required.

Palmatine Protects Against MSU-Induced Gouty Arthritis via Regulating the NF-κB/NLRP3 and Nrf2 Pathways.

Purpose: Gouty arthritis could be triggered by the deposition of monosodium uric acid (MSU) crystals. Palmatine (PAL), a protoberberine alkaloid, has been proven to possess compelling health-beneficial activities. In this study, we aimed to explore the effect of PAL on LPS plus MSU crystal-stimulated gouty arthritis in vitro and in vivo. Methods: PMA-differentiated THP-1 macrophages were primed with LPS and then stimulated with MSU crystal in the presence or absence of PAL. The expression of pro-inflammatory cytokines and oxidative stress-related biomarkers and signal pathway key targets were determined by ELISA kit, Western blot, immunohistochemistry and qRT-PCR, respectively. In addition, the anti-inflammatory and antioxidant activities of PAL on MSU-induced arthritis mice were also evaluated. Results: The results indicated that PAL (20, 40 and 80 µM) dose-dependently decreased the mRNA expression and levels of pro-inflammatory cytokines (interleukin-1beta (IL-1ß), IL-6, IL-18 and tumor necrosis factor alpha (TNF-α)). The levels of superoxide dismutase (SOD) and glutathione (GSH) were remarkably enhanced, while the level of malondialdehyde (MDA) was reduced. Western blot analysis revealed that PAL appreciably inhibited NF-κB/NLRP3 signaling pathways through inhibiting the phosphorylation of p-65 and IκBα, blocking the expression of NLRP3, ASC, IL-1ß and Caspase-1, as well as enhancing the antioxidant protein expression of Nrf2 and HO-1. In vivo, PAL attenuated MSU-induced inflammation in gouty arthritis, as evidenced by mitigating the joint swelling, and decreasing the productions of IL-1ß, IL-6, IL-18, TNF-α and MDA, while enhancing the levels of SOD and GSH. Moreover, PAL further attenuated the infiltration of neutrophils into joint synovitis. Conclusion: PAL protected against MSU-induced inflammation and oxidative stress via regulating the NF-κB/NLRP3 and Nrf2 pathways. PAL may represent a potential candidate for the treatment of gouty arthritis.

Differences in proteomic profiles between yak and three cattle strains provide insights into molecular mechanisms underlying high-altitude adaptation.

Yaks display unique properties of the lung and heart, enabling their adaptation to high-altitude environments, but the underlying molecular mechanisms are still largely unknown. In the present study, the proteome differences in lung and heart tissues were compared between yak (Bos grunniens) and three cattle strains (Bos taurus, Holstein, Sanjiang and Tibetan cattle) using the sequential window acquisition of all theoretical mass spectra/data-independent acquisition (SWATH/DIA) proteomic method. In total, 51,755 peptides and 7215 proteins were identified. In the lung tissue, there were 162, 310 and 118 differential abundance proteins (DAPs) in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. In the heart tissue, there were 71, 57 and 78 DAPs in Tibetan, Holstein and Sanjiang cattle compared to yak respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the DAPs were enriched for the retinol metabolism and toll-like receptor categories in lung tissue. The changes in these two pathways may regulate hypoxia-induced factor and immune function in yaks. Moreover, DAPs in heart tissues were enriched for cardiac muscle contraction, Huntington's disease, chemical carcinogenesis and drug metabolism-cytochrome P450. Further exploration indicated that yaks may alter cardiac function through regulation of type 2 ryanodine receptor (RyR2) and Ca2+ -release channels. The present results are useful to further develop an understanding of the mechanisms underlying adaptation of animals to high-altitude conditions.

Cystinosis induced by CTNS gene mutation: a rare disease study. / ç½•è§ç— ç ”ç©¶ï¼šCTNSåŸºå› çªå˜è‡´èƒ±æ°¨é ¸è´®ç§¯ç—‡.

A boy, aged 1 year and 6 months, was found to have persistent positive urine glucose at the age of 4 months, with polydipsia, polyuria, and growth retardation. Laboratory examinations suggested that the boy had low specific weight urine, anemia, hypokalemia, hyponatremia, hypomagnesemia, metabolic acidosis, glycosuria, acidaminuria, increased fractional excretion of potassium, and decreased tubular reabsorption of phosphate. X-ray examinations of the head, thorax, and right hand showed changes of renal rickets. The slit-lamp examination showed a large number of cystine crystals in the cornea. The genetic testing showed a suspected pathogenic homozygous mutation of the CTNS gene, C.922g>A(p.Gly308Arg). The boy was finally diagnosed with cystinosis. At the beginning of treatment, symptomatic supportive treatment was given to maintain the stability of the internal environment, and cysteamine tartaric acid capsules were used after diagnosis to remove cysteine. This article reported a case of cystinosis caused by CTNS gene mutation and summarized the etiology, clinical features, diagnosis, and treatment of this disease, which can provide a reference for the early diagnosis, treatment, and subsequent study of the disease.

SET and MYND domain-containing protein 3 inhibits tumor cell sensitivity to cisplatin.

Cisplatin resistance has been a major factor limiting its clinical use as a chemotherapy drug. The present study aimed to investigate whether SET and MYND domain-containing protein 3 (SMYD3), a histone methyltransferase closely associated with tumors can affect the sensitivity of tumors to cisplatin chemotherapy. Real time-qPCR, western blotting, the luciferase reporter, MTT and clonogenic assays were performed to detect the effects of SMYD3 on the chemotherapy capacity of cisplatin. In the present study, SMYD3 exhibited different expression patterns in MCF-7 and T47D breast cancer cells. In addition, this differential expression was associated with tumor cell resistance to cisplatin. Furthermore, SMYD3 knockdown following small interfering RNA transfection increased cisplatin sensitivity, whereas SMYD3 overexpression decreased cisplatin sensitivity. In addition, SMYD3 knockdown synergistically enhanced cisplatin-induced cell apoptosis. SMYD3 expression was downregulated during cisplatin treatment. In addition, transcriptional regulatory activities of SMYD3 3'-untranslated region were also downregulated. These results suggested that SMYD3 may affect cell sensitivity to cisplatin and participate in the development of cisplatin resistance, which is a process that may involve microRNA-124-mediated regulation.

BUB1 promotes proliferation of liver cancer cells by activating SMAD2 phosphorylation.

Budding uninhibited by benzimidazoles 1 (BUB1) is a mitotic checkpoint serine/threonine kinase that has been reported as an oncogene or tumor suppressor gene in various types of cancer, including breast cancer, pancreatic ductal adenocarcinoma, prostate and gastric cancers. However, its role in liver cancer remains unclear. The present study aimed to explore the biological function of BUB1 in liver cancer. The present study demonstrated that BUB1 mRNA expression levels and the intensity of immunohistochemical staining were significantly increased in liver cancer tissues compared with normal tissues. The role of BUB1 in cell proliferation was also determined. Overexpression of BUB1 significantly promoted cell proliferation, whereas knockdown of BUB1 expression inhibited the proliferation of liver cancer cell lines. In experiments investigating the underlying mechanism, overexpression of BUB1 increased the levels of SMAD2 phosphorylation, whereas knockdown of BUB1 reduced the levels of SMAD2 phosphorylation. Therefore, BUB1 may promote proliferation of liver cancer cells by activating phosphorylation of SMAD2, and BUB1 may serve as a potential target in the diagnosis and/or treatment of liver cancer.

Effects of RNAi-induced Skp2 inhibition on cell cycle, apoptosis and proliferation of endometrial carcinoma cells.

The aim of the current study was to investigate the underlying mechanism of S-phase kinase associated protein 2 (Skp2) gene inhibition by lentivirus-mediated RNA interference (RNAi) on the cell cycle, apoptosis and proliferation of endometrial carcinoma HEC-1-A cells. A lentivirus shRNA vector targeting Skp2 was constructed and transfected into HEC-1-A cells. HEC-1-A cells transfected with a scramble sequence were used as negative controls. The mRNA and protein expression of Skp2, p27, cyclin D1 and caspase-3 were detected via reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The effects of Skp2 inhibition on the cell cycle, apoptosis and proliferation of HEC-1-A cells were detected using flow cytometry and a cell counting kit-8. Skp2 co-expression data was analyzed using Oncomine and TCGA databases. The positive recombinant viral clones were identified via PCR and confirmed via sequencing. The mRNA and protein expression of Skp2 were significantly decreased in HEC-1-A cells transfected with the lentiviral vectors compared with the negative control. In addition, there were no significant changes in the mRNA expression of p27 and cyclin D1; however, the protein levels of p27 and cyclin D1 were upregulated and downregulated, respectively, in HEC-1-A cells transfected with lentiviral vectors compared with negative controls. RNAi-induced Skp2 inhibition exerted an anti-proliferative effect by inducing cell cycle arrest, however cell apoptosis was not significantly affected. In the TCGA database, Skp2 expression positively associated with IGF2R, IGF2BP3, IGFBP1 and CCNF, while Skp2 expression negatively associated with IGF2, IGFBP6, IGFBP7 and IGFBP3. RNAi-induced Skp2 inhibition upregulated the protein expression of p27 and downregulated the protein expression of cyclin D1. The expression of Skp2 in endometrial cancer may therefore be regulated by the insulin-like growth factor 1 receptor signaling pathway.

Anti-melanogenesis properties of condensed tannins from Vigna angularis seeds with potent antioxidant and DNA damage protection activities.

Condensed tannins contained in food are known to have many beneficial impacts on human health. In this study, we attempt to evaluate the structural features, antityrosinase effects, anti-melanogenesis properties, antioxidant activity and DNA damage protection activity of condensed tannins purified from the seeds of Vigna angularis (Willd.) Ohwi et Ohashi. MALDI-TOF MS, ESI-Full-MS, and HPLC-ESI-MS demonstrated that condensed tannins are composed of procyanidins, prodelphinidins and their gallates, among which procyanidins are the dominant components. As reversible and mixed-type inhibitors of tyrosinase, condensed tannins from V. angularis strongly inhibited the monophenolase and odiphenolase activities with IC50 values of 130.0 ± 0.5 and 35.1 ± 2.0 µg mL-1, respectively. What's more, condensed tannins had a good inhibitory effect on cell proliferation, cellular tyrosinase activity, and melanogenesis of B16 mouse melanoma cells. Based on fluorescence quenching analyses, these compounds were determined to be effective quenchers of the enzyme and its substrates. According to molecular docking, the strong interaction between condensed tannins and tyrosinase was mainly driven by hydrogen bonding and hydrophobic force. In addition, condensed tannins showed a powerful antioxidant capacity and DNA damage protection activity. Therefore, condensed tannins from V. angularis have feasible applications in food, medicine, and the cosmetics industry.

Mitogen-activated protein kinase inhibition enhances the antitumor effects of sporamin in human pancreatic cancer cells.

Sporamin, a sweet potato tuber storage protein, is a Kunitz-type trypsin inhibitor (TI) that has exhibited antitumor activity through poorly defined mechanisms in a number of types of tumor cells. The present study aimed to analyze the combined effects of sporamin and three mitogen-activated protein kinase (MAPK) inhibitors, PD98059, SP600125 and SB203580, on the pancreatic cancer cell line, PANC-1. Cell proliferation activity was assessed using a 3H-thymidine incorporation assay, and cell viability was analyzed using an MTT assay. Apoptosis was assayed by flow cytometry and fluorescence microscopy. Protein expression levels in PANC-1 cells were determined by western blotting. The results of this analysis demonstrated that sporamin induced a temporary increase in the phosphorylation of MAPKs, including phosphorylated extracellular signal regulated-kinase 1/2, phosphorylated c-Jun amino-terminal protein kinase 1/2 and phosphorylated p38-MAPK, in a concentration-dependent manner. However, treatment with MAPK inhibitors promoted the inhibition of cell proliferation and viability, and the induction of apoptosis in sporamin-treated PANC-1 cells. In conclusion, the present study demonstrated that MAPK inhibition enhanced the antitumor activity of sporamin in PANC-1 cells.

Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant dermatosis: Report of 4 cases.

BACKGROUND: Topical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases. OBJECTIVES: To determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis. OBSERVATIONS: We presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects. CONCLUSIONS: Topical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget's disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated.

Sporamin suppresses growth of human esophageal squamous cell carcinoma cells by inhibition of NF­κB via an AKT­independent pathway.

The aim of the present study was to determine whether sporamin, a trypsin inhibitor, suppresses the growth of human esophageal squamous cell carcinoma (ESCC) cells in vitro. Sporamin treatment led to the suppression of viability and proliferation of human ESCC cell lines, EC9706 and EC109, as determined by MTT and [3H] thymidine incorporation assays, respectively. Flow cytometry and fluorescence microscopy demonstrated that sporamin significantly induced apoptosis in EC9706 and EC109 cells. Western blotting demonstrated that sporamin downregulated the expression of Bcl­2 and Bcl­2 like 1, and upregulated the expression of Bcl­2­associated X in EC9706 and EC109 cells. In addition, marked inhibition of nuclear factor (NF)­κB activation was observed in sporamin­treated EC9706 and EC109 cells by an electrophoretic mobility shift assay. Sporamin treatment also resulted in reduced expression levels of phosphorylated (p)­NF­κB inhibitor α and nuclear NF­κB p65. However, the expression levels of p­protein inase (AKT) and its downstream target, p­p70 S6 kinase, were not markedly altered following sporamin treatment. In conclusion, sporamin may suppress the growth of human ESCC cells via NF­κB­dependent and AKT­independent mechanisms and may act as a promising natural therapeutic agent for the treatment of human ESCC.

ß-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-κB and activating Nrf2 pathways.

ß-Patchoulene (ß-PAE), a tricyclic sesquiterpene isolated from the essential oil of the leaves and stems of Pogostemon cablin (Blanco) Benth., has been reported to have potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of ß-PAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. ALI was induced by intracheal instillation of LPS into lung, and dexamethasone (DEX) was used as a positive control. Results indicated that pretreatment with ß-PAE significantly decreased the mortality rate of mice and lung W/D weight ratio, ameliorated lung pathological changes as compared to model group. Meanwhile, ß-PAE pretreatment markedly inhibited the increase of TNF-α, IL-6 and IL-1ß secretions in the bronchoalveolar lavage fluid, and prevented LPS-induced elevations of MPO activity and MDA level in the lung. Additionally, ß-PAE pretreatment significantly elevated miR-146a expression and suppressed the LPS-induced activation of NF-κB and expression of its mediated genes (TNF-α, IL-6 and IL-1ß). ß-PAE was also observed to markedly upregulate the Nrf2 and HO-1 expression and activate the antioxidant genes (NQO-1, GCLC and HO-1). Taken together, ß-PAE possessed protective effect against LPS-induced ALI, which might be associated with its differential regulation of NF-κB and Nrf2 activities and up-regulation of expression of miR-146a. The results rendered ß-PAE a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of ALI.

Age-related changes in CD4+CD25+FOXP3+ regulatory T cells and their relationship with lung cancer.

OBJECTIVES: CD4+CD25+FOXP3+ regulatory T cells (Treg) inhibit the anti-tumour immune response and reduce the effect of cancer immunotherapy. Although studies have demonstrated that the number and suppressive activity of Treg increase with age, it is not clear whether these changes correlate with a higher incidence of tumours in the elderly. This study was designed to explore the relationship between increase in CD4+CD25+FOXP3+ Treg and the higher risk of lung cancer in the elderly. METHODS: Seventy lung cancer patients and 60 sex- and age-matched controls were recruited. Both groups were divided into three subgroups based on their age (young, middle-aged, or elderly). The proportion of CD4+CD25+FOXP3+ /CD4+ T cells was detected using flow cytometry, and the level of FOXP3 mRNA in the peripheral blood was examined with real-time RT-PCR. RESULTS: The levels of CD4+CD25+FOXP3+/CD4+ T cells and FOXP3 mRNA were significantly higher in lung cancer patients than in healthy controls (t = 7.16, P < 0.01 and t = 3.65, P < 0.01, respectively). Within the healthy groups, the elderly group had larger proportion of CD4+CD25+FOXP3+ Treg (F = 32.54, P < 0.01) and higher FOXP3 mRNA expression (F = 4.76, P < 0.01) than their younger counterparts. Among the six subgroups, the elderly lung cancer patients exhibited the highest levels of both CD4+CD25+FOXP3+ Treg (11.81 ± 2.40%) and FOXP3 mRNA (3.14 ± 1.30). CONCLUSIONS: The accumulation of CD4+CD25+FOXP3+ Treg with age correlates well with the increasing incidence of lung cancer in the elderly.

Clinicopathological significance of SMAD4 loss in pancreatic ductal adenocarcinomas: a systematic review and meta-analysis.

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer mortality. Although advances have been made in understanding the pathogenesis of PDAC, the outcome still remains poor. The aim of this study is to conduct a meta-analysis to evaluate the precise association between SMAD4 loss and clinicopathological significance in PDAC. A literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, Odds Ratio or Hazard Ratio with corresponding confidence intervals was calculated and summarized. 12 relevant articles were included for full review in detail and meta-analysis. The frequency of SMAD4 protein loss was significantly increased in PDAC than in nonmalignant pancreatic tissue, Odd Ratio was 0.05 with 95% confidence interval 0.01-0.23, p<0.0001. SMAD4 loss was significantly associated with poor overall survival in patients with PDAC, Hazard Ratio was 0.61 with 95% confidence interval 0.38-0.99, p=0.05. SMAD4 loss was not correlated with the size, grades, and lymph node metastasis of PDAC. In conclusion, SMAD4 is a biomarker for the diagnosis of PDAC. SMAD4 loss is significantly related to poor prognosis in patients with PDAC.

Targeting Btk with ibrutinib inhibit gastric carcinoma cells growth.

Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.

[Epidemiological Studies on Echinococcosis in Kizilsu Kirgiz Autonomous Prefecture of Xinjiang].

Objective: To understand the prevalence and characteristics of echinococcosis in Kizilsu Kirgiz Autonomous Prefecture (abbreviated as Kizilsu) of Xinjiang, in the aim of providing evidence for prevention and treatment of echinococcosis. Methods: Sixty-two villages were selected as investigation spots from 19 towns in agricultural and pasturing areas of Ulugqat County, Artux City, Akto County, and Akqi County during 2011-2012. Ultrasound abdominal scan was performed in all residents in these spots to examine the occurance of echinococcosis. ELISA was performed to detect the echinococcosis-specific antibody in sera from children of 6-12 years and the antigen of Echinococcus granulosus in freshly-collected dog feces. Hydatid cysts in viscera of at slaughterhouses in the four spots were examined by touching and visual observation. Results: Ultrasound was conducted in 12 000 residents, among whom 60 were found to be positive for echinococcosis (echinococcosis granulosa), with a morbidity of 0.5%（60/12 000）. The morbidity in Ulugqat County was 1.1%（35/3 200）, significantly higher than that in Artux City（0.5%, 13/2 400）, Akto County（0.2%, 8/3 200）, and Akqi County（0.1%, 4/3 200）（χ2=4.92-24.79, P<0.05）. The morbidity was highest in residents ≥71 years（1.2%, 4/323）, followed by the age group of 0-10 years（0.9%, 3/350）, but with no significant difference among age groups（χ2=0.39-3.31, P＞0.05）. The serum antibody positive rate in children was 3.1%（230/7 338）, highest in Artux City（4.9%, 89/1 828） with significant difference in comparison to Akto County（2.9%, 56/1 927）, and Akqi County（0.7%, 11/1 639）（χ2=9.71, 54.34, P<0.05）. The hydatid cyst rate in livestock was 7.7%（291/3 769）, of which 97.3%（283/291） were in sheep. The antigen positive rate in dog feces was 3.3%（74/2 219）. Conclusion: The morbidity（1.1%） was highest in Ulugqat County and the antibody positive rate（4.9%） in children was highest in Artux City. Infection was found in livestock and dogs.

The gastroprotective effect of pogostone from Pogostemonis Herba against indomethacin-induced gastric ulcer in rats.

Pogostemonis Herba, known as "Guang-Huo-Xiang" in Chinese, has been widely used in the treatment of gastrointestinal dysfunction. Pogostone is one of the major constituents of Pogostemonis Herba. The aim was to scientifically evaluate the possible gastroprotective effect and the underlying mechanisms of pogostone against indomethacin-induced gastric ulcer in rats. Rats were orally treated with vehicle, lansoprazole (30 mg/kg) or pogostone (10, 20 and 40 mg/kg) and subsequently exposed to acute gastric lesions induced by indomethacin. Gross evaluation, histological observation, gastric mucosal superoxide dismutase activity, glutathione content, catalase activity, malonaldehyde level and prostaglandin E2 production were performed. Immunohistochemistry and reverse transcription polymerase chain reaction for cyclooxygenase-1 and cyclooxygenase-2, as well as terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, immunohistochemistry for heat-shock protein 70, B-cell lymphoma-2 and Bax were conducted. Results indicated that rats pretreated with pogostone showed remarkable protection from the gastric mucosa damage compared to vehicle-treated rats based on the ulcer index and inhibition percentage. Histologically, oral administration of pogostone resulted in observable improvement of gastric injury, characterized by reduction of necrotic lesion, flattening of gastric mucosa and alleviation of submucosal edema with hemorrhage. Pogostone pretreatment significantly raised the depressed activities of superoxide dismutase, glutathione and catalase, while reduced the elevated malonaldehyde level compared with indomethacin-induced group. Pogostone-pretreated group induced a significant increase in gastric mucosal prostaglandin E2 level and obvious up-regulation of protein levels and mRNA expressions of cyclooxygenase-1 and cyclooxygenase-2. Furthermore, antiapoptotic effect of pogostone was verified by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, and the apoptotic process triggered by pogostone involved the up-expression of heat-shock protein70 and B-cell lymphoma-2 protein, and suppression of Bax protein expressions in the ulcerated tissues. It is speculated that the gastroprotective effect of pogostone against indomethacin-induced gastric ulceration might be associated with its stimulation of cyclooxygenase-mediated prostaglandin E2, antioxidant and antiapoptotic effect.

The Relationship Between Lipoprotein-Associated Phospholipase A(2), Cholesteryl Ester Transfer Protein and Lipid Profile and Risk of Atherosclerosis in Women with Iron Deficiency Anaemia.

BACKGROUND: The relationship between lipoprotein-associated phospholipase A2 (Lp-PLA2), cholesteryl ester transfer protein (CETP), and risk of atherosclerosis in IDA women has not been fully clarified. The objective of this study was to investigate lipid-related atherogenic risk factors in women with IDA. METHODS: Eighty women with IDA and 80 age-matched healthy women as the control group were enrolled in the study. Serum lipid profile, Lp-PLA2, and CETP were determined. Correlations between lipid-related atherogenic risk factors were analyzed by Pearson's correlation analyses. RESULTS: TG levels were higher and HDL-C levels were lower in the IDA women. Lp-PLA2 activity, Lp-PLA2 concentration, and CETP concentration were higher in the IDA women. There were negative correlations between activity or concentration of Lp-PLA2 and hemoglobin level (r = -0.29 or r = -0.33, p < 0.05), as well as HDL-C level (r = -0.38 or r = -0.35, p < 0.05). Positive correlations were observed between Lp-PLA2 activity and Lp-PLA2 concentration and low-density lipoprotein cholesterol (LDL-C) level (r = 0.41 or r = 0.36 respectively, p < 0.05). CETP concentration was negatively correlated with hemoglobin (r = -0.56, p < 0.01) and HDL-C level (r = -0.35, p < 0.05) and positively correlated with triglyceride level (r = 0.34, p < 0.05). CONCLUSIONS: Increases in the levels of circulating CETP and Lp-PLA2 might partly play a role in the atherogenic disturbances in patients with IDA through increased susceptibility to lipid peroxidation.