Oral and injectable Marsdenia tenacissima extract (MTE) as adjuvant therapy to chemotherapy for gastric cancer: a systematic review.

BACKGROUND: Marsdenia tenacissima extract (MTE) is a phytochemical widely used as complementary therapy in cancer care. This systematic review was conducted to investigate the anticancer and detoxification effects of MTE, as an adjuvant therapy to chemotherapy, for treating gastric cancer. METHODS: Ten databases were searched to identify randomized controlled trials (RCTs) comparing oral or injectable MTE plus chemotherapy versus chemotherapy alone for treating gastric cancer up to May 1, 2019. In meta-analyses, proportional odds ratios (PORs) with 95% confidence intervals (CIs) were pooled for the ordinal outcomes using the generalized linear model, and risk ratios (RRs) with 95% CIs were pooled for dichotomous outcomes using the Mantel-Haenszel method. RESULTS: Seventeen RCTs with 1329 individuals were included, with a moderate to high risk of selection and performance bias. Compared to chemotherapy alone, MTE adjuvant therapy significantly improved the response to anticancer treatment (POR 2.01, 95% CI 1.60-2.53) and patients' performance status (POR 3.15, 95% CI 2.22-4.48) and reduce the incidences of chemotherapy-induced leukopenia (RR 0.66, 95% CI 0.56-0.78), thrombocytopenia (RR 0.64, 95% CI 0.48-0.86), anemia (RR 0.89, 95% CI 0.72-1.10), nausea/vomiting (RR 0.79, 95% CI 0.69-0.91), hepatic injury (RR 0.77, 95% CI 0.61-0.96), and peripheral neurotoxicity (RR 0.77, 95% CI 0.59-1.01). However, MTE did not significantly alleviate anemia, diarrhea, constipation, kidney injury, and oral mucosal lesions after chemotherapy. Incidence of nausea/vomiting was lower in patients receiving oral MTE than those receiving injectable MTE (RR 0.47 vs. 0.82, interaction P = 0.04). Heterogeneity was generally low among these outcomes. Three out of five RCTs that reported survival data supported the effects of MTE for prolonging progression-free and/or overall survival. No studies reported safety outcomes of MTE. CONCLUSIONS: The current evidence with limitations of risk of selection and performance bias suggests that MTE, as an adjuvant therapy to chemotherapy, is effective for inhibiting cancer growth and reducing incidences of multiple chemotherapy side effects. Oral MTE may be a better choice. Uncertainty remains regarding the effects of MTE on survival endpoints and the subgroup differences between acute and chronic use of MTE and between different chemotherapy regimens.

Altered brain functional network topology in Obsessive-Compulsive Disorder: A comparison of patients with varying severity of depressive symptoms and the impact on psychosocial functioning.

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with psychosocial impairment, which can be exacerbated by depressive symptoms. In this study, we employed graph theory analysis to investigate the association among neuroimaging, clinical features, and psychosocial functioning in OCD patients, with a specific focus on the differential impact of depressive symptoms. METHODS: 216 OCD patients were divided into two subgroups based on depressive symptoms. Resting-state functional MRI data were acquired from a subset of 106 OCD patients along with 77 matched healthy controls (HCs). We analyzed the topological characteristics of the entire brain and the cognition-related subnetworks and performed Pearson correlation analyses to further explore the relationship with psychosocial functioning. RESULTS: OCD patients with more severe depressive symptoms exhibited greater impairment across all dimensions of psychosocial functioning. Graph theory analysis revealed more pronounced reductions in network efficiency within the entire brain, the default mode network (DMN), and the cingulo-opercular network (CON) among patients with non or mild depressive symptoms. Lower nodal efficiency and degree centrality of the right superior temporal gyrus (STG) were found in OCD patients and these variables were positively correlated with psychosocial functioning impairment. CONCLUSIONS: This study revealed that the presence of depressive symptoms generally exacerbated psychosocial functioning impairment in OCD patients. Abnormalities in the functional integration of the entire brain, the DMN, and the CON in OCD patients may comprise the basis of cognitive deficits, while dysfunction of the right STG may affect the psychosocial functioning through its role in emotion, intention perception, and insight.

The concentration-dependent chemokine release and pro-apoptotic effects of neutrophil-derived alpha-defensin-1 on human bronchial and alveolar epithelial cells.

Defensins play a pivotal role in antimicrobial reactions, inflammatory responses, wound repair, and specific immunity. In inflammatory and infectious lung diseases, alpha-defensins are released from recruited neutrophils, and modulate a variety of lung cell functions. We found that human bronchial and alveolar epithelial cells treated with low and moderate concentrations (5 and 10 micro g/ml) of purified neutrophil-derived alpha-defensin-1 secreted more interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 in a dose- and time-dependent manner. Under moderate and high concentrations (10 and 20 micro g/ml) of alpha-defensin-1, we observed typical apoptotic changes in the lung epithelial cells after stimulation for 24 h. Furthermore, alpha-defensin-1 triggered lung cell detachment in a time- and dose-dependent manner at moderate and high concentrations. Prior to the detachment, caspase-3 activity significantly increased. On confocal laser microscopy, rapid translocation of alpha-defensin-1 to the endoplasmic reticulum (ER) was noted. These findings suggest that neutrophil-derived alpha-defensin-1 has pro-inflammatory and apoptotic effects in human bronchial and alveolar epithelial cells, which are concentration-dependent and may be associated with ER activity.