Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human Plasmodium falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, a protein integral to the host erythrocyte membrane and encoded by a member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also insert at the host membrane is unknown; their contributions to PSAC formation and other roles served are also unexplored. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog is colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular proteases, but CLAG8 and CLAG9 are protease resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with higher physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in the transcription of the remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake for specific solutes. We also report on the distinct transport properties of these knockout lines. Similar membrane topologies at the host membrane are consistent with each CLAG paralog contributing to PSAC, but other roles require further examination.
Chronic exposure to fluoride through drinking water has been linked to insulin resistance and resulting type 2 diabetes mellitus (T2DM). Here, we aim to study the impact of water fluoride levels on blood glucose and vitamin D levels. A hospital-based study was conducted on diabetic patients (n = 303) at All India Institute of Medical Sciences (AIIMS), Raebareli outstation patient department (OPD). The relationship between vitamin D or fasting blood glucose levels (BGLs) with water fluoride levels was estimated through Spearman's rank correlation. We found a significant negative correlation between water fluoride and vitamin D levels [rs = −0.777, p-value < 0.001] and a positive correlation between water fluoride and fasting BGLs [rs = 0.178, p-value 1.5 mg/L) had higher odds of severe vitamin D deficiency (odds ratio: 5.07, 95% CI: 1.9–13.2, p-value = 0.0009). The results demonstrate that vitamin D deficiency and fasting BGLs are significantly associated with water fluoride levels. This study signifies the role of fluoride toxicity in poor glycemic control and derived vitamin D deficiency. Vitamin D supplementation and the application of standard household water purification devices are recommended to tackle vitamin D deficiency in fluoride-endemic areas.
30 November 2019 in Journal of Medicinal Plants Research
Terminalia bellerica Roxb., commonly known as Beleric myrobalan, is a well-known large deciduous tree with various pharmaceutical properties. However, scientific information on T. bellerica, growing in India, as regards to its phytochemical constituents and pharmacological properties is very limited. With this in view, this study investigated the antioxidant, DNA protective and antibacterial activities of different parts (fruit pulp, seed and bark) of T. bellerica. Methanol (70%) and water (100% distilled water) were used for the extraction and analysis of total phenolic contents (TPC). Plant extracts were further screened for antibacterial activity against both gram (+) and gram (-) bacteria and minimum inhibitory concentration (MIC) values were calculated. Amongst the tested extracts, methanolic extract contained more TPC than aqueous extract. Methanolic fruit pulp (MEFP) showed lower IC50 (118.7 µg/ml) for free radical, (77.65 µg/ml) superoxide anion radical, (73.76 µg/ml) hydroxyl radical scavenging activity, (115.6 µg/ml) lipid peroxidation and (184.98 µg/ml) ferric thiocyanate assay. Methanolic extract also exhibited more potential DNA protective and antibacterial activity than aqueous extract. Furthermore, the correlation between TPC and antioxidant studies revealed that phenolics are mainly responsible for antioxidant, DNA protective and antibacterial activities of T. bellerica. This study suggests that the methanolic extract of T. bellerica could be a potential source of natural antioxidants. Key words: Terminalia bellerica, antioxidative, DNA protective, antibacterial.
Background: Anemia is a most common health issue in Indian population mainly due to nutritional deficiencies. A number of factors contribute in anemia which is further categorized based on various parameters in hematological indices and microscopic examination. Methods: A retrospective study has been carried out on the patients (n = 1332) in a retrospective study on the patients (n = 1332) in Raebareli district to determine prevalence of anemia and subsequent categorization into normocytic, microcytic and macrocytic based on complete blood count (CBC) profile and blood smear. Results: This study demonstrates 15.54% patients were diagnosed for anemia and more than half of the total anemic patients (55.07%) were found to be suffered from macrocytosis which was found significantly more prevalent among male (65.17%) compare to female (38.38%) patients. Conclusions: Several factors may contribute to macrocytosis among male population including alcoholism in Raebareli region. However, female patients were found almost equally susceptible to all three forms of anemia: normocytic, microcytic and macrocytic. This study provides a key insight into prevalence and possible causes of different types of anemia in this region which may be useful for implementation of government health programs to counter this problem and provide better treatment plans.