Effect of Ascorbic Acid on the Degradation of Cyanocobalamin and Hydroxocobalamin in Aqueous Solution: A Kinetic Study

The degradation kinetics of 5 × 10⁻⁵ M cyanocobalamin (B₁₂) and hydroxocobalamin (B_12b) in the presence of ascorbic acid (AH₂) was studied in the pH range of 1.0–8.0. B₁₂ is degraded to B_12b which undergoes oxidation to corrin ring cleavage products. B_12b alone is directly oxidized to the ring cleavage products. B₁₂ and B_12b in degraded solutions were simultaneously assayed by a two-component spectrometric method at 525 and 550 nm without interference from AH₂. Both degrade by first-order kinetics and the values of the rate constants at pH 1.0–8.0 range from 0.08 to 1.05 × 10⁻⁵ s⁻¹ and 0.22–7.62 × 10⁻⁵ s⁻¹, respectively, in the presence of 0.25 × 10⁻³ M AH₂. The t_1/2 values of B₁₂ and B_12b range from 13.7 to 137.5 h and 2.5–87.5 h, respectively. The second-order rate constants for the interaction of AH₂ with B₁₂ and B_12b are 0.05–0.28 × 10⁻² and 1.10–30.08 × 10⁻² M⁻¹ s⁻¹, respectively, indicating a greater effect of AH₂ on B_12b compared to that of B₁₂. The k_obs–pH profiles for both B₁₂ and B_12b show the highest rates of degradation around pH 5. The degradation of B₁₂ and B_12b by AH₂ is affected by the catalytic effect of phosphate ions on the oxidation of AH₂ in the pH range 6.0–8.0.KEY WORDS: ascorbic acid, cyanocobalamin, degradation, hydroxocobalamin, kinetics, two-component spectrometry     

Ethnobotany of the Balti community,Tormik valley,Karakorum range,Baltistan, Pakistan

Background

Limited health facilities and malnutrition are major problems in the Karakorum Range of Northern Pakistan, often resulting in various human disorders. Since centuries, however, local communities in these areas have developed traditional methods for treating various ailments and local foods capes that can be significant for devising public health and nutritional policies. This study was intended to document the ethnobotanical knowledge of the local peoples in the Tormik Valley, especially in the medical and food domains.

Methods

Field trips were undertaken in 14 different villages of the study area from 2010 to 2012. Ethnobotanical data were gathered using semi-structured interviews and group conversation with 69 informants. Details about local uses of plant species were recorded along with demographic characteristics of the visited communities. Relative frequency citation index (RFCi) and preference ranking index (PRi) tools were applied to determine the cultural significance of the reported species.

Results

Sixty-three plant species, with a predominance of Asteraceae and Fabaceae family members, as well as their detailed folk uses were documented. Forty-three percent of the species were used to treat various diseases, 21 % were consumed as wild fruits and vegetables and 53 % of the species had multipurpose applications. Thymus linearis Benth, Hippophae rhamnoides ssp. turkestanica L. and Convolvulus arvensis L. were found to be the most utilized medicinal plant species, i.e. those with significant RFCi values (0.54, 0.51 and 0.48, respectively). Betula utilis D. Don was the most versatile taxon (seven different ways of utilization); being this species a common and easily accessible subalpine tree and then under anthropogenic pressure, the implementation of concrete strategies aimed at its in-situ and ex-situ conservation is strongly recommended.

Conclusion

The valleys in the Karakorum Mountains in the Northern Pakistan host significant Traditional Knowledge on local food and medicinal plant species, which need to be reconsidered and cautiously re-evaluated by ethnopharmacologists, and public health/nutrition actors. Furthermore, germane trans-disciplinary investigations are suggested to ensure the dynamic conservation of precious local knowledge systems, as well as plant diversity in Pakistani mountain regions.

     

Molecular phylogeny and diversity of penaeid shrimps (Crustacea: Decapoda) from South-East Asian waters

The decapod family Penaeidae comprises most of the economically important marine shrimp species. Its members are widespread throughout the world, with its highest species diversity centred in the Indo-West Pacific region. Despite this importance, their taxonomy, classification and phylogeny are not yet settled due in part to incongruence among hypotheses proposed from molecular versus morphological studies. In this study, using a thorough taxonomic sampling of especially the South-East Asian species, we aim to (a) utilize a reconstructed phylogeny to test the monophyly of the Penaeidae and its currently recognized genera and (b) explore its species diversity in South-East Asian waters. To infer the phylogeny, a combined gene data set (including 109 ingroup and six outgroup taxa) of mitochondrial genes, COI and 16S rRNA, and two nuclear genes, NaK and PEPCK, was utilized. To explore its diversity, another data set that included 371 COI gene sequences (231 newly generated and 140 retrieved from public sources) was compiled and subsequently analysed with two different tools (ABGD and bPTP) for species delimitation. Other than supporting the non-monophyly of the Penaeidae with the Sicyoniidae nested within the penaeid tribe Trachypenaeini, the genera Penaeus, Mierspenaeopsis and Parapenaeopsis were also revealed to be polyphyletic. Our species delimitation analysis inferred that 94 putative species actually existed within the 71 morphospecies reviewed, indicating an underestimated biodiversity in this family and the potential presence of new species within the following morphospecies: Kishinouyepenaeopsis cornuta, K. incisa, Mierspenaeopsis sculptilis, M hardwicki, Parapenaeopsis coromandelica and Penaeus monodon.     

Contribution of P2X4 receptor in pain associated with rheumatoid arthritis: a review

Purinergic Signalling - Pain is the most common symptom reported by patients with rheumatoid arthritis (RA) even after the resolution of chronic joint inflammation. It is believed that...     

Synthesis and antimalarial activity of novel chiral and achiral benzenesulfonamides bearing 1, 3, 4-oxadiazole moieties

A series of new benzenesulfonamides, most of which are chiral, incorporating 1, 3, 4-oxadiazole and amino acid moieties have been synthesized. Some of these compounds were screened for antimalarial activity and also evaluated for their ability to inhibit hem polymerization. The electrophoretic analysis indicated that one compound was effective in inhibiting the degradation of hemoglobin. The synthesized compounds were tested in mice infected with Plasmodium berghei. These derivatives have the potential for the development of novel antimalarial lead compounds.     

Risk assessment of heavy metal and metalloid toxicity through a contaminated vegetable (Cucurbita maxima) from wastewater irrigated area: A case study for a site-specific risk assessment in Jhang,Pakistan

The present research was conducted in district Jhang, Pakistan, to evaluate the concentration of metals/metalloids in soil and pumpkin (Cucurbita maxima) irrigated with domestic wastewater. Data revealed that the levels of metals and metalloids in soil samples from two different sites were below the safe limits except Cd, whereas, in the vegetable, the concentrations of As, Se, Ni, Mo, Pb, Mn, and Cu were above the safe limits. The levels of 12 metals and metalloids in the soil were ranged between 0.14 to 22.76 mg/kg at site-I and 0.16 to 22.13 mg/kg at site-II. The levels of these metals in the vegetable were found 0.35 to 61.13 mg/kg at site-I and 0.31 to 53.63 mg/kg at site-II. The transfer factor at both sites was highest for As and Co. The pollution load index recorded for Se, Cu, Cd, Mo, Pb, and Co was greater than 1. The daily intake of As, Mn, and Mo was above the oral reference dose, which reflects that the intake of pumpkin is not safe for the inhabitants of the selected sites. The control measures should be taken to phytoextract heavy metals and metalloids from polluted sites so as to reduce the health risks.     

Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic approach

In our present study, binding between an important anti renal cancer drug temsirolimus and human transferrin (hTF) was investigated employing spectroscopic and molecular docking approach. In the presence of temsirolimus, hyper chromaticity is observed in hTF in UV spectroscopy suggestive of complex formation between hTF and temsirolimus. Fluorescence spectroscopy revealed the occurrence of quenching in hTF in the presence of temsirolimus implying complex formation taking place between hTF and temsirolimus. Further, the mode of interaction between hTF and temsirolimus was revealed to be static by fluorescence quenching analysis at 3 different temperatures. Binding constant values obtained employing fluorescence spectroscopy depicts strong interaction between hTF and temsirolimus; temsirolimus binds to hTF at 298 K with a binding constant of .32 × 10⁴ M^?1 implying the strength of this interaction. The negative Gibbs free energy obtained through quenching experiments is evident of the fact that the binding is spontaneous. CD spectra of hTF also showed a downward shift in the presence of temsirolimus as compared with free hTF implying complex formation between hTF and temsirolimus. Molecular docking was performed with a view to find out which residues are key players in this interaction. The importance of our study stems from the fact it will provide an insight into binding pattern of commonly administered renal cancer drug with an important protein that plays a pivotal role in many physiological processes.     

Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome

Two groups of tau, 3R- and 4R-tau, are generated by alternative splicing of tau exon 10. Normal adult human brain expresses equal levels of them. Disruption of the physiological balance is a common feature of several tauopathies. Very early in their life, individuals with Down syndrome (DS) develop Alzheimer-type tau pathology, the molecular basis for which is not fully understood. Here, we demonstrate that Dyrk1A, a kinase encoded by a gene in the DS critical region, phosphorylates alternative splicing factor (ASF) at Ser-227, Ser-234, and Ser-238, driving it into nuclear speckles and preventing it from facilitating tau exon 10 inclusion. The increased dosage of Dyrk1A in DS brain due to trisomy of chromosome 21 correlates to an increase in 3R-tau level, which on abnormal hyperphosphorylation and aggregation of tau results in neurofibrillary degeneration. Imbalance of 3R- and 4R-tau in DS brain by Dyrk1A-induced dysregulation of alternative splicing factor-mediated alternative splicing of tau exon 10 represents a novel mechanism of neurofibrillary degeneration and may help explain early onset tauopathy in individuals with DS.