Naringin inhibits the biofilms of metallo-β-lactamases (MβLs) producing Pseudomonas species isolated from camel meat

Food producing animals harbouring bacteria carrying drug resistance genes especially the metallo-beta-lactamase (MBL) pose high risk for the human population. In addition, formation of biofilm by these drug resistant pathogens represents major threat to food safety and public health. In this study, metallo-β-lactamases (MβLs) producing Pseudomonas spp. from camel meat were isolated and assessed for their biofilm formation. Further, in vitro and in silico studies were performed to study the effect of flavone naringin on biofilm formation against isolated Pseudomonas spp. A total of 55% isolates were found to produce metallo-β-lactamase enzyme. Naringin mitigated biofilm formation of Pseudomonas isolates up to 57%. Disturbed biofilm architecture and reduced the colonization of bacteria on glass was observed under scanning electron microscope (SEM) and confocal laser scanning microscope (CLSM). The biofilm related traits such as exopolysaccharides (EPS) and alginate production was also reduced remarkably in the presence of naringin. Eradication of preformed biofilms (32–60%) was also observed at the respective 0.50 × MICs. Molecular docking revealed that naringin showed strong affinity towards docked proteins with binding energy ranging from −8.6 to −8.8 kcal mol⁻¹. Presence of metallo-β-lactamase producers indicates that camel meat could be possible reservoir of drug-resistant Pseudomonas species of clinical importance. Naringin was successful in inhibiting biofilm formation as well as eradicating the preformed biofilms and demonstrated strong binding affinity towards biofilm associated protein. Thus, it is envisaged that naringin could be exploited as food preservative especially against the biofilm forming food-borne Pseudomonas species and is a promising prospect for the treatment of biofilm based infections.     

Observations on the floristic,life-form,leaf-size spectra and habitat diversity of vegetation in the Bhimber hills of Kashmir Himalayas

Vegetation analysis provides the prerequisites to understand the overall community structure and function of any ecosystem and is a fundamental requirement for the precise evaluation of biodiversity. Although many studies have assessed floristic attributes of specific areas, there are still unexplored regions, as is the case of the mountain region in the Kashmir Himalayas. Current research highlighted the recent findings of the scientific characterization of floristic and ecological aspects on the forest flora found in the Bhimber hills, Pakistan. Floristically, a total of 93 species belonging to 80 genera in 41 families were recorded. The species distribution patterns across the families were disproportionate with half of the species contributed by 8 families and 25 families were monotypic. Based on the floristic analysis, Asteraceae was the largest family with 12% of species followed by Poaceae with (11%) species. PAST software, a multivariate ecological community analysis was used to classify the species similarities and differences among the different habitat types. According to the habitat wise distribution, 21% of species were growing in the natural forest habitat, while 15% of species were dispersed in highly distributed habitats along roadsides and 8% on pedestrians. In terms of functional diversity, the herbaceous growth form was dominant (58%). The biological spectrum revealed therophytes as the dominant life form as it indicates the disturbed habitat vegetation. The phytogeographical analysis revealed that the maximum (69%) species were native, while the minimum (31%) species were exotic. Thus, the study of these functional and habitat diversity patterns can significantly improve our understanding of the ecological aspects of the flora in the geographical location. This information may additionally be useful in devising management plans to ensure sustainable utilization and better management of forest landscapes in this Himalayan region.     

Perspectives of pluripotent stem cells in livestock

The recent progress in derivation of pluripotent stem cells(PSCs)from farm animals opens new approaches not only for reproduction,genetic engineering,treatment and conservation of these species,but also for screening novel drugs for their efficacy and toxicity,and modelling of human diseases.Initial attempts to derive PSCs from the inner cell mass of blastocyst stages in farm animals were largely unsuccessful as either the cells survived for only a few passages,or lost their cellular potency;indicating that the protocols which allowed the derivation of murine or human embryonic stem(ES)cells were not sufficient to support the maintenance of ES cells from farm animals.This scenario changed by the innovation of induced pluripotency and by the development of the 3 inhibitor culture conditions to support na?ve pluripotency in ES cells from livestock species.However,the long-term culture of livestock PSCs while maintaining the full pluripotency is still challenging,and requires further refinements.Here,we review the current achievements in the derivation of PSCs from farm animals,and discuss the potential application areas.     

Molecular simulation of the Kv7.4[ΔS269] mutant channel reveals that ion conduction in the cavity is perturbed due to hydrophobic gating

Mutations in the voltage-gated potassium channel Kv7.4 (encoded as KCNQ4) lead to the early onset of non-syndromic hearing loss, which is significant during language acquisition. The deletion of the S269 pore residue (genetic Δ mutation) in Kv7.4 has been reported to be associated with hearing loss. So far, there is no mechanistic understanding of how this mutation modulates channel function. To understand the role of S269 in ion conduction, we performed molecular dynamics simulations for both wild type and ΔS269 mutant channels. Simulations indicate that the ΔS269 mutation suppresses the fluctuations in the neighboring Y269 residue and thereby consolidates the ring formed by I307 and F310 residues in the adjacent S6 helixes in the cavity region. We show that the long side chains of I307 near the entrance to the cavity form a hydrophobic gate. Comparison of the free energy profiles of a cavity ion in Kv7.4 and Kv7.4[ΔS269] channels reveals a sizable energy barrier in the latter case, which suppresses ion conduction. Thus the simulation studies reveal that the hydrophobic gate resulting from the ΔS269 mutation appears to be responsible for sensorineural hearing loss.     

Galinsosides A and B,bioactive flavanone glucosides from Galinsoga parviflora

Galinsosides A (1) and B (2), new flavanone glucosides together with two known flavanones, 7,3′,4′-trihydroxyflavanone (3) and 3,5,7,3′,4′-pentahydroxyflavanone (4) have been isolated from an ethyl acetate- soluble fraction of Galinsoga parviflora. Their structures were assigned on the basis of spectral studies. Compound 1 showed significant antioxidant and urease inhibitory activity while compound 2 was moderately active. On the other hand, 2 showed inhibitory potential against α-glucosidase.     

Antifungal and antibacterial activities of Taxus wallichiana Zucc

Current study was undertaken to evaluate the in vitro antifungal and antibacterial potential of methanol extract and subsequent fractions obtained after partitioning in organic solvents with variable polarity of the aerial parts of the tree Taxus wallichiana Zucc. Traditionally, this plant is often used in folk medicines in Pakistan for treating microbial infections. In order to rationalize the traditional use, methanol extracts of leaf, bark, and heartwood of Taxus wallichiana Zucc. were tested against six bacteria and six fungal strains using the Hole diffusion and macro-dilution methods. All extracts and fractions displayed significant antimicrobial effect. Only three fungal strains, Trichophyton longifusus, Microspoum canis, and Fusarium solani were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. In case of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were susceptible to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. Comparison results were carried out using imipinem, miconazole and amphotericin B as standard antibiotics.     

In vitro cytotoxic,antibacterial, antifungal and urease inhibitory activities of some N4- substituted isatin-3-thiosemicarbazones

A series of 15 previously reported N⁴-substituted isatin-3-thiosemicarbazones 3a-o has been screened for cytotoxic, antibacterial, antifungal and urease inhibitory activities. Compounds 3b, 3e and 3n proved to be active in cytotoxicity assay; 3e exhibited a high degree of cytotoxic activity (LD₅₀ = 1.10 × 10^{? 5} M). Compound 3h exhibited significant antibacterial activity against B. subtilis, whereas compounds 3a, 3k and 3l displayed significant antifungal activity against one or more fungal strains i.e. T. longifusus, A. flavus and M. canis. In human urease enzyme inhibition assay, compounds 3g, 3k and 3m proved to be the most potent inhibitors, exhibiting relatively pronounced inhibition of the enzyme. These compounds, being non-toxic, could be potential candidates for orally effective therapeutic agents to treat certain clinical conditions induced by bacterial ureases like H. pylori urease. This study presents the first example of inhibition of urease by isatin-thiosemicarbazones and as such provides a solid basis for further research on such compounds to develop more potent inhibitors.     

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.     

Photodegradation and Stabilization of Betamethasone-17 Valerate in Aqueous/Organic Solvents and Topical Formulations

The effects of solvent [acetonitrile, methanol, and acetonitrile/water mixture (20:80, v/v)], buffer concentration (phosphate buffer, pH 7.5), ionic strength and commonly employed adjuvants on the photodegradation of betamethasone-17 valerate in cream and gel formulations have been studied on exposure to UV light (300–400 nm). A validated high-performance liquid chromatography method has been used to determine the parent compound and its photodegraded products. The photodegradation data in the studied solvents showed greater decomposition of the drug in solvents with a lower dielectric constant. A comparatively higher rate of photodegradation was observed in the cream formulation compared to that for the gel formulation. The kinetic treatment of the photodegradation data revealed that the degradation of the drug follows first-order kinetics and the apparent first-order rate constants for the photodegradation reactions, in the media studied, range from 1.62 to 11.30 × 10⁻³ min⁻¹. The values of the rate constants decrease with increasing phosphate concentration and ionic strength which could be due to the deactivation of the excited state and radical quenching. The second-order rate constant (k′) for the phosphate ion-inhibited reactions at pH 7.5 has been found to be 5.22 × 10⁻² M⁻¹ s⁻¹. An effective photostabilization of the drug has been achieved in cream and gel formulations with titanium dioxide (33.5–42.5%), vanillin (21.6–28.7%), and butyl hydroxytoluene (18.2–21.6%).Key words: betamethasone-17 valerate, creams and gels, kinetics, photodegradation, photostabilization     

Correction for Irrelevant Absorption in Multicomponent Spectrophotometric Assay of Riboflavin, Formylmethylflavin, and Degradation Products: Kinetic Applications

In the spectrophotometric assay of multicomponent systems involved in drug degradation studies, some minor or unknown degradation products may be present. These products may interfere in the assay and thus invalidate the results due to their absorption in the range of analytical wavelengths. This interference may be eliminated by the application of an appropriate correction procedure to obtain reliable data for kinetic treatment. The present study is based on the application of linear and non-linear irrelevant absorption corrections in the multicomponent spectrophotometric assay of riboflavin and formylmethylflavin during the photolysis and hydrolysis studies. The correction procedures take into account the interference caused by minor or unknown products and have shown considerable improvement in the assay data in terms of the molar balance. The treatment of the corrected data has led to more accurate kinetic results in degradation studies.