Baicalin Enhances Chemosensitivity to Doxorubicin in Breast Cancer Cells via Upregulation of Oxidative Stress-Mediated Mitochondria-Dependent Apoptosis.

Doxorubicin (Dox) is an effective anthracycline anticancer drug. However, recent studies have revealed that Dox resistance is a highly critical issue, and a significant reason for treatment failure. Baicalin is a flavonoid component in the roots of Scutellaria baicalensis Georgi; however, whether baicalin can increase chemosensitivity in breast cancers is still unclear. In this study, we found that cellular apoptosis occurs when excessive intracellular ROS is generated, triggered by the dual intervention of baicalin and doxorubicin, which increases intracellular calcium [Ca2+]i concentrations. Increased [Ca2+]i concentrations decrease the mitochondrial membrane potential (△Ψm), thereby causing cellular apoptosis. Pretreatment with NAC (ROS inhibitor) or BATBA (Ca2+ chelator) reduces baicalin-induced chemosensitivity. The findings of this study demonstrate that the effect of baicalin on Dox treatment could enhance cytotoxicity toward breast cancer cells via the ROS/[Ca2+]i-mediated intrinsic apoptosis pathway-thus potentially lessening the required dosage of doxorubicin, and further exploring associated mechanisms in combined treatments for breast cancer clinical interventions in the future.

Effects of Exercise in Patients Undergoing Chemotherapy for Head and Neck Cancer: A Pilot Randomized Controlled Trial.

BACKGROUND: Cisplatin administration may induce muscle atrophy, thereby reducing the fitness level of patients with head and neck cancer (HNC). To date, only animal studies have been conducted to test the effectiveness of exercise interventions in diminishing side effects of cisplatin. AIM: To determine whether exercise training improves physical fitness and health-related quality of life (HRQoL) in patients receiving chemotherapy for Head & Neck (H&N). MATERIAL AND METHODS: This pilot-randomized controlled trial was conducted on 57 participants receiving chemotherapy for HNC. The participants were randomized into an exercise group and a control group. The exercise group received moderate-intensity combined aerobic, resistance and flexibility exercises three times a week for eight weeks during chemotherapy. The control group received no specific information regarding exercise. The outcome measures including body composition, muscle strength, balance, flexibility, cardiovascular fitness and health-related quality of life (HRQoL) were assessed at baseline and eight weeks following baseline. RESULTS: The body composition (body fat percentage, p = 0.002; skeletal muscle percentage, p = 0.008), dynamic balance (p = 0.01), muscle strength (upper extremity, p = 0.037; lower extremity, p = 0.025) and HRQoL (p = 0.001) showed a significant difference between the exercise group and the control group eight weeks following baseline. Significant deteriorations were noted in flexibility, muscle strength, cardiovascular fitness and several domains of HRQoL scale in the control group at eight weeks following baseline. CONCLUSIONS: This study found that a combined aerobic, resistance and flexibility exercise program during chemotherapy may improve physical fitness (i.e., muscle strength, balance, flexibility and body composition) and HRQoL and alleviate the deterioration of cardiovascular fitness in patients with HNC. Further research studies with large sample sizes are warranted to investigate the long-term effects of exercise in this population.

Immune Dysfunction and Coinfection with Human Immunodeficiency Virus and Schistosoma japonicum in Yi People.

OBJECTIVE: To explore the association between infections with HIV and Schistosoma japonicum, and to determine the influences of the HIV-S. japonicum coinfections on the immune system of Yi people. METHODS: A block design study was conducted in a Yi county in southwestern China, one of the endemic areas of both HIV/AIDS and S. japonicum in China. All participants were screened for HIV antibodies and S. japonicum antibodies (SjAb) and were classified into four groups: HIV(+)/S. japonicum(-), HIV(-)/S. japonicum (+), HIV(+)/S. japonicum(+), and HIV(-)/S. japonicum(-). RESULTS: There were significant differences among the four groups in both CD4+ T lymphocytes and CD8+ T lymphocytes, but no significant difference in CD3+ T lymphocytes. Both the CD4+ T lymphocyte counts and the ratio of CD4+/CD8+ were lower in HIV-infected people compared with those uninfected. People infected with S. japonicum had increased CD4+ T lymphocyte counts but reduced CD8+ T lymphocyte counts. Similarly, the ratio of CD4+/CD8+ was higher in S. japonicum-infected people compared with those uninfected. People coinfected with HIV and S. japonicum had lower CD4+ T lymphocyte counts, lower ratio of CD4+/CD8+, and higher CD8+ T lymphocyte counts compared with those infected with HIV only or S. japonicum only. People infected with HIV only and those coinfected with HIV and S. japonicum had a higher level of IFN-γ compared with people with no infection. There were no significant differences between people infected with HIV only and with S. japonicum only in the levels of IFN-γ and IL-10. CONCLUSIONS: People coinfected with HIV and S. japonicum might have a suppressed immune function because of a decrease in CD4+ T lymphocyte counts, a lowered ratio of CD4+/CD8+, and an increase in CD8+ T lymphocyte counts. Coinfection with HIV and S. japonicum would alter the level of IFN-γ in plasma.

The Three Gorges Dam: Does the Flooding Time Determine the Distribution of Schistosome-Transmitting Snails in the Middle and Lower Reaches of the Yangtze River, China?

BACKGROUND: Schistosomiasis is one of the most devastating tropical diseases in the world. Oncomelania hupensis is the only intermediate host of Schistosoma japonicum, and its growth and development are sensitive to environmental factors. The Three Gorges Dam has substantially altered the water level in the Yangtze River. This study focused on the impact of the flooding time on the occurrence of Oncomelania snails in Hunan Province, China. METHODS: The data regarding Oncomelania snails were collected from the Schistosomiasis Atlas of the People's Republic of China. Air temperature, hours of daylight and relative humidity from 1995 to 2002 were collected from the China Meteorological Data Sharing Service System. The data for rainfall and days inundated with water were collected from the Hunan flood control information system and hydrological stations in Hunan Province. A generalized additive model was used to estimate the impact of these factors on the presence or absence of snails. RESULTS: The number of days inundated with water in the areas with snails ranged from 56 to 212 days. However, 82 percent of the areas without snails were inundated with water less than 60 days. The lowest air temperature in a year in the areas without snails ranges from -2.88 °C to -2.10 °C, and the range was from -2.88 °C to -2.34 °C for areas with snails. Annual rainfall in the areas with snails ranged from 989 to 1565 mm, and the range was from 1230 mm to 1647 mm for the areas without snails. The results from the generalized additive model showed that the number of days inundated with water, lowest air temperature in a year, annual rainfall, days of daily rainfall greater than 0.1 mm, and hours of daylight were the factors that significantly affect the occurrence of snails in Hunan Province, China. CONCLUSIONS: The number of days inundated with water may be a key factor determining the geographical distribution of Oncomelania snails in Hunan Province and the favorable number of days inundated with water for the survival of snails ranges from about 2 to 7 months.

[Advances in researches of molluscicidal microorganisms against Oncomelania hupensis].

The elimination of Oncomelania hupensis snails is important to schistosomiasis control. Recently, the application of molluscicidal organisms is considered as a safe and efficient method for snail elimination. In order to provide scientific evidences for effective control of O. hupensis and schistosomiasis, this paper summarizes the researches of molluscicidal microorganisms against O. hupensis.

Differential autophagic cell death under stress with ectopic cytoplasmic and mitochondrial-specific PPP2R2B in human neuroblastoma cells.

Protein phosphatase 2A is one of four major classes of serine/threonine phosphatases. Overexpression of brain-specific regulatory subunit PPP2R2 in neuron cells is implicated in pathogenesis. The alternative splicing of PPP2R2B encodes two isoforms. They are subunit of cytoplasmic specific Bß1 and mitochondria-targeted Bß2. The two constructs were transfected into human neuroblastoma cells, SK-N-SH, respectively, and the stable clones overexpressing either Bß1 or Bß2 established. We have reported that Bß2 clones are sensitive to reactive oxygen species (ROS) treatment by inducing autophagic cell death. To study more on the onset of neuropathogenesis under strain, both clones were exposed to different environmental stress, e.g. starvation and endoplasmic reticulum (ER) stress. To learn how PPP2R2B overexpression responds to starvation, cells were incubated in Hank's buffered salt solution of deprived nutrient. Cell death was induced in Bß1 clones after 6 h starvation, but not in Bß2 clones. The pharmacological inhibitor, Bafilomycin A1, rescued the cell death while suppressing autophagy. On the other hand, to assess how cells respond to ER stress, the cells were treated with 0.1 µM of N-glycosylation inhibitor, tunicamycin (TM). In contrast with Bß1, the apoptotic cell death appeared in Bß2 after 48 h treatment. The formation of autophagolysosome was detected in Bß2 following 12 h treatment with TM as evidenced by lysotracker and GFP-LC3 staining for fluorescence microscopy analysis. The autophagy inhibitor, 3-methyladenine, salvaged the final apoptosis. The stable cell lines with ectopically transfected PPP2R2B genes encoding isoforms of brain-specific regulatory subunit exhibit distinct apoptosis under different stressors. The induced autophagic apoptotic cell death is related to mitochondrial membrane potential drop and ROS generation. Disturbance of autophagy alleviates the induced cell death. The results promised a good model for understanding the onset in pathogenesis under stress in neuron cells with aberrant PPP2R2B expression.

Oxidative stress promotes autophagic cell death in human neuroblastoma cells with ectopic transfer of mitochondrial PPP2R2B (Bbeta2).

BACKGROUND: The multifunctional protein phosphatase 2A (PP2A) is a heterotrimeric serine/threonine protein phosphatase composed of a scaffolding, catalytic and regulatory subunits. By modifying various downstream signal transducers, the aberrant expression of the brain-targeted regulatory subunit PPP2R2B is associated with the onset of a panel of neuronal disorders. The alternatively splicing of PPP2R2B encodes two regulatory subunit isoforms that determine cellular distribution of the neuron-specific holoenzyme to mitochondria (Bbeta2) and cytoplasm (Bbeta1), respectively. RESULTS: Human neuroblastoma cells were transfected with PPP2R2B constructs encoding the complete sequences of Bbeta2 and Bbeta1, respectively. The colonies with antibiotic resistance were selected as stable cell lines. Both ectopic Bbeta1 and Bbeta2 clones exhibited characteristics of autophagy. To test how cells respond to reactive oxygen species generators, the cells were treated with either hydrogen peroxide or t-butyl hydroperoxide and Bbeta2 clones induced cell death. Suppression of autophagy using either RNA interference of the essential autophagy gene or pharmacological inhibitor rescued cell death caused by oxidative stress. CONCLUSIONS: Cells with ectopically expressed mitochondria-targeted regulatory subunit PPP2R2B of the holoenzyme PP2A were shown predisposed to autophagy and oxidative stress induced cell death that is related to apoptosis. The results promised a model for studying the mechanism and function of aberrant PPP2R2B expression in neuronal cells. The work provided a new target for understanding and prevention of neuropathogenesis.