Labdane-type diterpenoids and sesquiterpenes from Curcuma aromatica and their nitric oxide inhibitory activity in lipopolysaccharide-stimulated RAW264.7 macrophages.

One new labdane-type diterpenoid, 3ß,15-dihydroxylabda-8(17),12E-dien-16,15-olide (1) named curcumatin and twelve known compounds, coronarin D (2), isocoronarin D (3), (E)-labda-8(17),12-diene-15,16-dial (4), zerumin A (5), (E)-labda-8(17),12-dien-15,16-dioic acid (6), furanodiene (7), linderazulene (8), zedoarol (9), zedoarondiol (10), germacrone-1,10-epoxide (11), germacrone-4,5-epoxide (12), and zingiberenol (13) were isolated from the ethanol extract of the roots of Curcuma aromatica Salisb. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, and comparing with the NMR data reported in the literature. Compounds 2, 5, and 13 significantly inhibited the nitric oxide production effect in LPS-stimulated RAW 264.7 macrophages with IC50 values of 8.8 ± 1.7, 4.0 ± 0.9, and 6.2 ± 0.4 µM, respectively.

Narciclasine suppresses esophageal cancer cell proliferation and migration by inhibiting the FAK signaling pathway.

Esophageal cancer (EC) is one of the malignant cancer with pool survival due to the limited therapeutic and drug-resistance. Narciclasine, a natural compound from Lycoris sanguinea possesses antitumor and anti-inflammatory properties. However, the mechanisms underlying the growth-inhibitory effect of narciclasine against EC have not yet been elucidated. Experimental evidences indicated that narciclasine treatment significantly affected the distribution of FAK and its phosphorylation, resulting in proliferation inhibition and migration inhibition of EC. Our study also showed that narciclasine treatment triggered DNA damage and inhibited DNA replication, leading to cell cycle arrest and apoptosis. Further mechanistic studies indicated that narciclasine inhibited EC cell proliferation and migration through FAK/JNK and p38 pathway. Altogether, these findings suggest that narciclasine could be a potential novel chemotherapeutic agent for esophageal cancer cell proliferation and migration.

Anticancer Activity of Lesbicoumestan in Jurkat Cells via Inhibition of Oxidative Stress-Mediated Apoptosis and MALT1 Protease.

This study explores the potential anticancer effects of lesbicoumestan from Lespedeza bicolor against human leukemia cancer cells. Flow cytometry and fluorescence microscopy were used to investigate antiproliferative effects. The degradation of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) was evaluated using immunoprecipitation, Western blotting, and confocal microscopy. Apoptosis was investigated using three-dimensional (3D) Jurkat cell resistance models. Lesbicoumestan induced potent mitochondrial depolarization on the Jurkat cells via upregulated expression levels of mitochondrial reactive oxygen species. Furthermore, the underlying apoptotic mechanisms of lesbicoumestan through the MALT1/NF-κB pathway were comprehensively elucidated. The analysis showed that lesbicoumestan significantly induced MALT1 degradation, which led to the inhibition of the NF-κB pathway. In addition, molecular docking results illustrate how lesbicoumestan could effectively bind with MALT1 protease at the latter's active pocket. Similar to traditional 2D cultures, apoptosis was markedly induced upon lesbicoumestan treatment in 3D Jurkat cell resistance models. Our data support the hypothesis that lesbicoumestan is a novel inhibitor of MALT1, as it exhibited potent antiapoptotic effects in Jurkat cells.

1-Methoxylespeflorin G11 Protects HT22 Cells from Glutamate-Induced Cell Death through Inhibition of ROS Production and Apoptosis.

This study aimed to investigate the neuroprotective effects of 1-methoxylespeflorin G11 (MLG), a pterocarpan, against glutamate-induced neurotoxicity in neuronal HT22 hippocampal cells. The protective effects of MLG were evaluated using MTT assay and microscopic analysis. The extent of apoptosis was studied using flow cytometric analysis performed on the damaged cells probed with annexin V/propidium iodide. Moreover, mitochondrial reactive oxygen species (ROS) were assessed using flow cytometry through MitoSOXTM Red staining. To determine mitochondrial membrane potential, staining with tetramethylrhodamine and JC-1 was performed followed by flow cytometry. The results demonstrated that MLG attenuates glutamate-induced apoptosis in HT22 cells by inhibiting intracellular ROS generation and mitochondrial dysfunction. Additionally, MLG prevented glutamate-induced apoptotic pathway in HT22 cells through upregulation of Bcl-2 and downregulation of cleaved PARP-1, AIF, and phosphorylated MAPK cascades. In addition, MLG treatment induced HO-1 expression in HT22 cells. These results suggested that MLG exhibits neuroprotective effects against glutamate-induced neurotoxicity in neuronal HT22 cells by inhibiting oxidative stress and apoptosis.

Transmission of highly pathogenic avian influenza in the nomadic free-grazing duck production system in Viet Nam.

The presence of free-grazing ducks (FGD) has consistently been shown to be associated with highly pathogenic avian influenza virus (HPAIV) H5N1 outbreaks in South-East Asia. However, the lack of knowledge about the transmission pathways limits the effectiveness of control efforts. To address this gap, we developed a probabilistic transmission model of HPAIV H5N1 in the nomadic FGD production system in Viet Nam, assuming different scenarios to address parameter uncertainty. Results suggested that HPAIV H5N1 could spread within the nomadic FGD production system, with an estimated flock-level effective reproduction number (re) ranging from 2.16 (95% confidence interval (CI): 1.39-3.49) to 6.10 (95%CI: 3.93-9.85) depending on the scenario. Indirect transmission via boats and trucks was shown to be the main transmission route in all scenarios. Results suggest that re could be reduced below one with 95% confidence if 86% of FGD flocks were vaccinated in the best-case scenario or 95% in the worst-case scenario. If vaccination was combined with cleaning and disinfection of transport vehicles twice a week, vaccination coverage could be lowered to 60% in the best-case scenario. These findings are of particular relevance for prioritising interventions for effective control of HPAIV in nomadic free-grazing duck production systems.

Antiproliferative Pterocarpans and Coumestans from Lespedeza bicolor.

Chromatographic purification of a methanol extract of the roots of Lespedeza bicolor led to the isolation of four new pterocarpans (1-4), two new coumestans (6 and 7), two new arylbenzofurans (8 and 9), and the known pterocarpan 1-methoxyerythrabyssin II (5). Their structures were identified using NMR spectroscopy, UV spectroscopy, and mass spectrometry. Cytotoxicity assays showed that compounds 1-9 exerted antiproliferative effects on blood cancer cells. Of these compounds, 1 and 6 induced mitochondrial depolarization and induced apoptosis in Jurkat cells. These compounds promoted cell death by inducing cell-cycle arrest at the G1 stage, reducing levels of BCL2, and increasing cleavage of PARP-1. These findings indicate that 1 and 6 are possible lead compounds for the treatment of human leukemia cells via intracellular signaling.

Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells.

Betula platyphylla bark has been evaluated for the treatment of dermatitis, inflammatory conditions, and cancer. Diarylheptanoids are the major constituents of the B. platyphylla bark and possess various pharmacological effects. Our previous study confirmed the selective antiproliferative effect of platyphylloside (BPP) isolated from B. platyphylla on colon cancer and leukemic cells using 60 different cancer cell lines from thr National Cancer Institution (NCI). In line with previous reports, this study focuses on the apoptotic pathway of BPP, a phenolic glycoside composed of two aromatic rings joined by a seven-carbon chain. Cytotoxicity assays in solid tumor and blood cancer cell models demonstrated that BPP possesses potent antiproliferative activity. The level of apoptosis increased with BPP treatment, causing cell cycle arrest at the G1 phase along with the downregulation of IκBα phosphorylation and BCL-2, as well as upregulation of cleaved caspase 3 and BAX proteins. In addition, BPP displayed potent mitochondrial depolarization effects in Jurkat cells. The combined findings revealed that the cytotoxic effects of BPP were mediated by intracellular signaling, possibly through a mechanism involving the upregulation of mitochondrial reactive oxygen species (ROS). Thus, BPP could be a potential multitarget therapeutic agent in leukemia and colon cancer.

Pain incidence, assessment, and management in Vietnam: a cross-sectional study of 12,136 respondents.

OBJECTIVE: To describe the rate and demographics of pain among Vietnamese people in 48 provinces and describe the impact of pain on individuals, levels of satisfaction with treatment results, and behavior of pain sufferers. METHODS: The cross-sectional study was conducted in adults presenting to outpatient clinics throughout 48 provinces in Vietnam and were randomly selected for inclusion in this study. A physician trained to administer a questionnaire in a standardized fashion interviewed each patient and collected data regarding gender, age, career, acute and chronic pain, diagnoses, treatment, and satisfaction with treatment. RESULTS: There were 12,136 respondents (50.65% male and 49.35% female) from 48 of the 63 provinces in Vietnam. About 86.53% of respondents reported experiencing pain that affected their daily lives, with 24.10% complaining of acute pain and 62.43% having chronic pain. About 67.71% reported pain that affected job performance. Headache was the most common complaint in 35.43% of the respondents. Fewer than half (43.35%) of all patients with pain sought help from a doctor; only a quarter (27.50%) sought help within 1 month of experiencing that pain. A majority (61.98%) of patients who did seek help were satisfied with treatment results. The median cost of treatment was between 150 and 250 USD. CONCLUSION: Pain severe enough to impact patients' daily lives is common in Vietnam. Treatment costs are a significant economic burden and may help explain why only a minority of patients seek treatment. Access to lower cost, effective treatment for pain should be improved.

Community knowledge, attitudes, and practices toward rabies prevention in North Vietnam.

In recent years, despite the accessibility to vaccines (both for humans and animals), rabies remains a problem in many areas of Vietnam. While the number of rabies deaths decreased by 90% from 1994 to 2003, the number of rabies deaths increased from 2004 to 2007. In 2007, the number of rabies victims was 2-3 times higher than in 2003 and 131 people died as a result of rabies. In order to better understand Knowledge, Attitudes, and Practices (KAP) toward rabies in areas of both high and low incidence of rabies mortality in Vietnam, and KAP between pet and non-pet owners, a cross-sectional study was carried out by administering a structured questionnaire to 585 respondents from selected households in Thanh Son District-Phu Tho Province and Viet Yen District-Bac Giang Province, Vietnam. KAP in both high and low incidence areas, especially in groups with pets, need to be improved, particularly regarding treatment practices after a dog-bite and recommended pet care. We recommend not only enhanced IEC activities, but also the development of a Behavior Change Communication Strategy (BCC).

Herpes simplex virus 2 infection in women attending an antenatal clinic in Fuzhou, China.

Genital herpes caused by herpes simplex virus (HSV) infection is one of the most prevalent sexually transmitted infections (STIs) and the most common cause of genital ulcer disease (GUD) in developed and developing countries. The monitoring of HSV-2 seroprevalence in pregnant women can identify women at a higher risk of HIV and of neonatal HSV transmission. Very few data are available on type specific seroprevalence of HSV-2 in China, with only one previous study from southern China. Consequently, we conducted a survey to determine type specific seroprevalence of HSV-2 and associated risk factors in Fuzhou City, eastern China.