Target ROS to induce apoptosis and cell cycle arrest by 5,7-dimethoxy-1,4-naphthoquinone derivative

The 1,4-naphthoquinone derivatives bearing 5,7-dimethoxyl moiety were designed, synthesized, and tested as the antitumor agents against five human cancer cell lines (A549, Hela, HepG2, NCI-H460 and HL-60). All the compounds are described herein for the first time. The structure-activity relationships indicated that the presence of chlorine atom at the 2-position was crucial for the antiproliferative activity. Further, the electrochemical properties of the representative compounds (7e, 8e and 9e) were evaluated and a definite correlation between the redox potential and the antiproliferative activity. The most potent compound 9e displayed significant anti-leukemic activity with IC₅₀ value of 3.8?μM in HL-60 cells and weak cytotoxicity with IC₅₀ of 40.7?μM in normal cells WI-38. In mechanistic study for 9e, the increased numbers of apoptotic cells and increased cell population at G2/M phase correlated with ROS generation. Together, our results suggested that the derivatives of 2-chlorine-1,4-naphthoquinone might be the promising candidates for the treatment of promyelocytic leukemia.     

In vitro insulin-like actions of human growth hormone: a study with an insulin antibody

When polyclonal insulin antibodies were preincubated with either adipose tissue from hypophysectomized rats or adipocytes from normal rats, human growth hormone failed to stimulate glucose oxidation. Removal of insulin from adipocytes through incubation with pyruvate at pH 7.0, followed by washing three times, also abolished subsequent in vitro insulin-like action of hGH. Administration of the same insulin antibody to hypophysectomized rats 30 minutes prior to injection of hGH did not inhibit the insulin-like activity of the hGH as measured by its ability to decrease serum glucose and non-esterified fatty acid levels. It is concluded that the in vitro promotion of glucose oxidation by hGH requires insulin. Because of the uncertainty of complete removal of insulin in intact animals, such a conclusion cannot be made regarding in vivo insulin-like action of hGH.     

Getting the Data Flowing: Lessons Learned from Existing Reporting Systems in the Forestry Sector in Indonesia for REDD+ MRV

In the context of REDD+, Measurement, Reporting and Verification (MRV) is one way to manage forest change information. A national carbon and non-carbon database will be used in REDD+ to negotiate compensation schemes with the international community. Much of this data will be collected at the local level, thus a reporting system that can integrate these locally collected data into the national database is crucial. In this paper we compare and draw lessons from three existing local to national reporting systems that include the participation of local communities: 1) the government extension services, 2) the government owned forestry company, and 3) a private logging company in Indonesia, and provide recommendations for REDD+ reporting systems. The results suggest that the main desired conditions for effective data flow are: benefits to motivate local participation, based on contributions to reporting activities; simple data format and reporting procedures to allow local participation in the reporting process, and to support data aggregation at the national level; a facilitator to mediate data aggregation at the village level to ensure data consistency, completeness and accuracy; and a transparent and clear data flow. Under these conditions, continuous, accountable and consistent data flow from the local level will reach the national level where it can be fully utilized.     

Clinical Forms of Canine Visceral Leishmaniasis in Naturally Leishmania infantum–Infected Dogs and Related Myelogram and Hemogram Changes

Hematological analysis has limited applications for disease diagnosis in Leishmania infantum–infected dogs, but it can be very important in evaluating the clinical forms of the disease and in understanding the evolution of canine visceral leishmaniasis (CVL) pathogenesis. Recently, we demonstrated that alterations in leucopoiesis and erythropoiesis are related to clinical status and bone marrow parasite density in dogs naturally infected by L. infantum. To further characterize these alterations, we evaluated the association between the hematological parameters in bone marrow and peripheral blood alterations in groups of L. infantum–infected dogs: asymptomatic I (AD-I: serum negative/PCR+), asymptomatic II (AD-II: serum positive), oligosymptomatic (OD), and symptomatic (SD). Results were compared with those from noninfected dogs (NID). The SD group was found to present a decrease in erythropoietic lineage with concomitant reductions in erythrocytes, hemoglobin, and hematocrit parameters, resulting in anemia. The SD group also had increased neutrophils and precursors and decreased band eosinophils and eosinophils, leading to peripheral blood leucopenia. In the AD-II group, lymphocytosis occurred in both the peripheral blood and the bone marrow compartments. The SD group exhibited lymphocytosis in the bone marrow, with lymphopenia in the peripheral blood. In contrast, the AD-I group, showed no significant changes suggestive of CVL, presenting normal counts in bone marrow and peripheral blood. Our results showed for the first time that important changes in hematopoiesis and hematological parameters occur during ongoing CVL in naturally infected dogs, mainly in symptomatic disease. Taken together, our results based on myelogram and hemogram parameters enable better understanding of the pathogenesis of the anemia, lymphocytosis, and lymphopenia, as well as the leucopenia (eosinopenia and monocytopenia), that contribute to CVL prognosis.     

Autogamy of an endangered species: Loropetalum subcordatum (Hamamelidaceae)

The reproductive biology of Loropetalum subcordatum was studied. The floral phenology, pollen histochemistry, pollen-ovule ratio (P/O), pollen viability and floral visitors were investigated and determined. Assisted pollination experiments were carried out to examine the breeding system of L. subcordatum. Scanning electron microscopy (SEM) and fluorescence microscopy (FM) were employed to check the pollen germination and the growth of pollen tubes. Results were obtained as follows: (1) The flowering period of L. subcordatum was from September to the next February with a peak at September-October; the longevity of a single flower was 4-6 days. (2) L. subcordatum was protogynous, and pollen grains could be found on self-stigmata when the anthers opened 12-24 h after petals unrolling. (3)The pollen viability (MTT test) maintained for ca. 26 hours; the pollen was starchless; the P/O was 8420±720.86 (n=10); no nectar secretion was observed. (4) Thrips (Thrips sp.) were the only floral visitors observed but which seldom moved among inflorescences, thus played limited role in pollination. (5) Fruit sets of untreated bagged (5.30±1.83%) and hand assisted cross pollinated flowers (6.67±1.91%) were not significantly different from that of open flowers (4.79±1.45%). (6) SEM and FM observations proved that pollen germinated on self-stigmata and pollen tubes growed in self-styles. The results indicated that L. subcordatum was facultatively autogamous and without apomixes. The possibility of outcrossing and the protogyny might indicate that the species was originally a crosser. Flowers pollinated in September-October usually start ovule growth in next summer, and set mature fruits in next October (after the next flowering peak), suggesting the occurrence of retard embryo development. The possibility that autogamy in Hamamelidaceae could have been developed from fly pollination was also discussed.     

Mussaenda lancipetala X. F. Deng & D. X. Zhang,a new species of Rubiaceae from China

Mussaenda lancipetala X. F. Deng & D. X. Zhang, a new species of Rubiaceae from Yunnan Province, Southwestern China, is described and illustrated. The new species is characterized by its reverse herkogamous sexual system, its ovate-lanceolate corolla lobes with caudate apex, and corolla tube covered with sparse farinose pubescence, by which it is clearly distinguished from other species of Mussaenda.     

Body measurements correlation and x-ray imaging of three Hystrix javanica fetuses in different fetal development stages

Hystrix javanica is endemic species in Indonesia. Study about fetal development of Hystrix javanica are very rare because of sample limitation. This study was carried out to describe the morphometrics and x-ray analysis of three fetuses in different stage to give basic information about fetal development of Hystrix javanica. Three fetus samples fixed in Bouin’s solution was used in this study. Observation was carried out to identify the characteristic of three fetus samples. This included the pattern of hair, body measurements, body volume, and body weight. X-ray analysis was carried out to know the ossification process in the fetal development. Statistical analysis was carried out using Microsoft 365® Excel program software. Three fetus samples had different specific hair pattern, that was hairless, smooth hairs, and smooth hairs with dense-non dense pattern. Body volume of 1^st, 2^nd, and 3^rd fetus were 23mL, 90mL, and 170mL, respectively. Body weight of 1^st, 2^nd, and 3^rd fetus were 19.5g, 79.22g, and 153.18g, respectively. Pearson’s correlation analysis shown strong relationship between total body length, front body length, back body length, horizontal body diameter, vertical body diameter, head length, and head diameter against body volume and body weight of three fetuses. Significant positive correlation was shown between horizontal body diameter, vertical body diameter, and head diameter against body volume and body length with P value < 0.05. Faint radiopaque images showed in the 2^nd fetus sample and strong radiopaque images showed in the 3^rd fetus sample. Radiopaque images were identified in the teeth, cranium, vertebrae, and extremities bones. In this study we concluded that there was a specific hair pattern in different fetal stage. All body measurements have positive correlation with body volume and body weight and x-ray analysis shown that the ossification of the bone was started to happen while the smooth hair was growth.     

Novel complex Re-Arrangement of ARG1 commonly shared by unrelated patients with Hyperargininemia

Background

Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutations were point mutations and a few others deletions or insertions.

Objective

This study aims at identifying the disease-causing mutation in the ARG1 gene of Malaysian patients with hyperargininemia.

Methodology

We employed a series of PCR amplifications and direct sequencing in order to identify the mutation. We subsequently used quantitative real-time PCR to determine the copy number of the exons flanking the mutation. We blasted our sequencing data with that of the reference sequence in the NCBI in order to obtain positional insights of the mutation.

Results

We found a novel complex re-arrangement involving insertion, inversion and gross deletion of ARG1 (designated g.insIVS1 + 1899GTTTTATCAT;g.invIVS1 + 1933_ + 1953;g.delIVS1 + 1954_IVS2 + 914;c.del116_188;p.Pro20SerfsX4) commonly shared by 5 patients with hyperargininemia, each originating from different family. None of the affected families share known relationship with each other, although four of the five patients were known to have first-cousin consanguineous parents.

Conclusion

This is the first report of complex re-arrangement in the ARG1. Further analyses showing that the patients have shared the same geographic origin within the northeastern part of Malaysia prompted us to suggest a simple molecular screening of hyperargininemia within related ethnicities using a long-range PCR.