Protection against Klebsiella pneumoniae Using Lithium Chloride in an Intragastric Infection Model

Intragastric Klebsiella pneumoniae infections of mice can cause liver abscesses, necrosis of liver tissues, and bacteremia. Lithium chloride, a widely prescribed drug for bipolar mood disorder, has been reported to possess anti-inflammatory properties. Using an intragastric infection model, the effects of LiCl on K. pneumoniae infections were examined. Providing mice with drinking water containing LiCl immediately after infection protected them from K. pneumoniae-induced death and liver injuries, such as necrosis of liver tissues, as well as increasing blood levels of aspartate aminotransferase and alanine aminotransferase, in a dose-dependent manner. LiCl administered as late as 24 h postinfection still provided protection. Monitoring of the LiCl concentrations in the sera of K. pneumoniae-infected mice showed that approximately 0.33 mM LiCl was the most effective dose for protecting mice against infections, which is lower than the clinically toxic dose of LiCl. Surveys of bacterial counts and cytokine expression levels in LiCl-treated mice revealed that both were effectively inhibited in blood and liver tissues. Using in vitro assays, we found that LiCl (5 μM to 1 mM) did not directly interfere with the growth of K. pneumoniae but made K. pneumoniae cells lose the mucoid phenotype and become more susceptible to macrophage killing. Furthermore, low doses of LiCl also partially enhanced the bactericidal activity of macrophages. Taken together, these data suggest that LiCl is an alternative therapeutic agent for K. pneumoniae-induced liver infections.     

2005-2009年新建县晚期血吸虫病患者治疗救助

目的掌握新建县晚期血吸虫病患者治疗救助情况。方法收集2005-2009年新建县晚期血吸虫病患者治疗救助数据,采用《江西省晚期血吸虫病人治疗救助信息管理系统》录入并统计。结果 636例患者中,男女性别比1.19∶1,平均年龄61.52±11.2岁。患者以腹水型为主,占93.71%,其中切脾术后患者占32.38%,IHA阳性率31.6%,HBsAg阳性率24.37%,复治率44.50%,临床治愈率43.53%,好转率55.94%,病死率5.97%。结论晚期血吸虫病治疗救助取得了改善患者症状、缓解病情和提高生活质量的效果。     

Functional variant of CHI3L1 gene is associated with neck metastasis in oral cancer

Objectives

Oral cancer is the most common head and neck malignancy, and it is associated with a high recurrence rate and lymph node metastasis potential. YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein that serves as a biomarker in several diseases. It also plays a crucial role in regulating many characteristics of cancer, such as cell growth, migration, anti-apoptosis, and angiogenesis. Accumulating evidence supports the link between single-nucleotide polymorphisms (SNPs) and oral cancer, but no report on the association between CHI3L1 polymorphisms and oral cancer is available. Thus, the present study evaluated the contribution of CHI3L1 SNPs to oral cancer susceptibility and clinicopathology.

Materials and methods

This study recruited a total of 2362 subjects, comprising 1190 healthy male controls and 1172 male patients with oral cancer. Allelic discrimination of the CHI3L1 polymorphisms − 1371 G>A (rs6691378), − 247 G>A (rs10399805), − 131 C>G (rs4950928), and + 2950 T>C (rs880633) was assessed through real-time polymerase chain reaction.

Results

We detected a significant association of rs10399805 and rs6691378 with the risk of oral cancer (AOR, 1.537; 95% CI, 1.089–2.168; p = 0.014; AOR, 1.561; 95% CI, 1.131–2.156; p = 0.007, respectively) after adjustment for three potential confounders, smoking, betel nut chewing, and alcohol consumption. Moreover, we found that oral cancer patients carrying the homozygous A/A genotype of the rs10399805 (p = 0.035) or rs6691378 polymorphism (p = 0.023) showed a significantly lower risk of lymph node metastasis. Moreover, according to the Genotype-Tissue Expression database, the rs10399805 and rs6691378 polymorphisms in the promoter region were associated with decreased levels of CHI3L1 mRNA.

Conclusions

In conclusion, we found that the homozygous mutant allele of rs10399805 and rs6691378 appeared to have significantly lower risk of lymph node metastasis and associated with its mRNA levels in oral cancer.

Clinical relevance

The CHI3L1 polymorphisms rs10399805 and rs6691378 may act as biomarkers for predicting lymph node metastasis in oral cancer patients.

     

Variations in bovine milk oligosaccharides after calving using p-aminobenzoic ethyl ester closed-ring labeling and negative ion electrospray LC/MS/MS

A strategy was proposed to analyze bovine milk oligosaccharides using p-aminobenzoic ethyl ester (ABEE) closed-ring labeling and C18 capillary liquid chromatography negative ion electrospray tandem mass spectrometry. Linkage specific fragment ions were used to identify oligosaccharide isomers. By constructing the mass chromatograms using linkage specific fragment ions, isomers were differentiated based on m/z values as well as temporal separation provided by liquid chromatography. In addition to disialyllactose and the single isomer lacto-N-neohexaose, four pairs of linkage isomers including 3′/6′-sialyllactose (3′/6′-SL), 3′/6′-sialyllactosamine (3′/6′-SLN), 3′/6′-sialylgalactosyl-lactose (3′/6′-SGL), and lacto-N-tetraose/lacto-N-neotetraose (LNT/LNnT) in bovine milk were investigated. Variations of bovine milk oligosaccharides in a lactation period of 72 h after calving were studied. Sialylated oligosaccharide was found to be distinctively more abundant in milk of the first 24 h, decreasing in successive milkings. For the first time, the variation of lacto-N-tetraose in bovine milk was reported.     

Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study

European Archives of Psychiatry and Clinical Neuroscience - Studies have indicated thalamus-related network dysfunction in schizophrenia and psychotic disorders. However, whether thalamus-related...     

Mechanisms of Panax ginseng in preventing rat pheochromocytoma cells from apoptosis

Aims of the study

Although ginseng root possesses dominant central therapeutic effects and has recently undergone investigations for treating different neuronal diseases, most of its mechanisms are still unknown. Therefore, the neuroprotective mechanisms of ginseng were studied.

Materials and methods

The protection afforded by different methanol extracts of Panax ginseng (PG) was tested in a serum deprivation-induced apoptotic model using neuronal-like pheochromocytoma (PC12) cells. An MTT assay, annexin V-FITC staining, and Western blots were, respectively, applied to identify the viability of cells, the apoptotic form of cell death, and the activity of antiapoptotic signaling.

Results

The known antiapoptotic PI3-K/Akt and MEK/ERK pathways in this system were ruled out due to failure of LY 294002 and PD 98059 to block the protection by PG. A protein kinase A (PKA) inhibitor was found to block the protection by PG and PG-induced CREB phosphorylation, suggesting that the PKA/CREB pathway mediates the protective effect of PG. Downregulation of classical and novel PKCs failed to block the protection by PG, while an atypical PKC inhibitor blocked protection by PG.

Conclusions

PKA and atypical PKC are important for the protection afforded by PG in preventing serum deprivation-induced PC12 cell apoptosis.     

Ligusticum chuanxiong as a potential neuroprotectant for preventing serum deprivation-induced apoptosis in rat pheochromocytoma cells: Functional roles of mitogen-activated protein kinases

Ethnopharmacological relevance

Ligusticum chuanxiong (LC) as a common component in many traditional Chinese medicinal formulas and decoctions has been used to treat different central nervous diseases, suggesting a neuroprotective function.

Aim of the study

To investigate the functional roles of mitogen-activated protein kinases (MAPKs) in mediating the neuroprotection of LC.

Materials and methods

Different extractions of LC were applied with or without MAPK inhibitor to test their protection against serum deprivation-induced apoptosis in rat neuronal-like pheochromocytoma (PC12) cells as revealed by an MTT assay or Hoechst staining. Western blot was used to identify the activations of MAPKs.

Results

The most effective butanol extraction (LC-BuOH) was used in the following experiments. LC-BuOH reversed serum deprivation-induced decreased phosphorylation of extracellular signal-regulated kinase (ERK) and increased phosphorylation of c-Jun NH₂-terminal kinase (JNK) and p38, the family of MAPKs. A PKA inhibitor, blocked the protection of LC-BuOH and partially blocked LC-BuOH-induced alterations in MAPKs, suggesting that the LC-BuOH regulates MAPKs through both PKA-dependent and -independent pathways. Although PD 98059, an inhibitor of MEK which activates ERK, blocked LC-BuOH-induced ERK phosphorylation, it did not block the protection of LC-BuOH.

Conclusions

LC-BuOH mediates protection by suppressing JNK/p38 instead of activating ERK activity.     

Alkaline Phosphatase: Does it have a Role in Predicting Hepatocellular Carcinoma Recurrence?

Backgrounds  

Surgical resection remains the first line of treatment for earlier stages of hepatocellular carcinoma (HCC), and it offers the best prognosis for long-term survival. Nevertheless, the recurrence rates after resection are still high in reports. Therefore, it is still essential to explore any potential prognostic factors to attain relatively longer-term survival of HCC patients.     

Predictors of Long-Term Disease-Free Survival After Resection of Hepatocellular Carcinoma: Two Decades of Experience at Chang Gung Memorial Hospital

Background: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. A high incidence of recurrence after hepatectomy is the most important cause of unsatisfactory results after resection of HCC. This study aimed to determine the clinicopathologic factors for predicting survival >5 years without recurrence in HCC patients treated with hepatectomy.Methods: The clinical features of 46 patients with surgically resected HCC who survived >5 years without recurrence (group A) were reviewed. Also, comparison was made with the clinical features and factors influencing the outcome of 1046 cases of resected HCC who survived <5 years both with and without recurrence and for >5 years with recurrence (group B).Results: Of 1092 cases of surgically resected HCC, 46 (4.5%) survived >5 years without recurrence. Univariate analysis revealed that absence of vascular invasion, satellite lesions, low histological grading of HCC, a lower rate of underlying liver cirrhosis, wider resection margins, and an uneventful postoperative course were frequent in group A patients compared with group B patients. Moreover, multivariate stepwise logistic regression analysis identified an absence of satellite lesions and an uneventful postoperative course as the two main independently significant predictors of HCC patients undergoing hepatectomy with long-term disease-free survival. The 1-, 3-, 5-, and 10-year survival rates of group A patients were 100%, 100%, 100%, and 84.1%, whereas those of group B patients were 73.5%, 47.9%, 29.0%, and 21.2%, respectively.Conclusions: An absence of satellite lesions and an uneventful postoperative course are the two main independent predictors for long-term disease-free survival in HCC patients undergoing hepatic resection.