A Possible Connection Between Antidiabetic & Antilipemic Properties of Psoralea corylifolia Seeds and the Trace Elements Present: A LIBS Based Study

Psoralea corylifolia (PC), a medicinal plant, is used in traditional medicine to treat diabetes. Purpose of the research was to examine the antidiabetic and antilipemic potential of PC and to determine the relationship between its antidiabetic potential and the trace elements present. Wistar rats (150–200 g) with fasting blood glucose (FBG) of 80–110 mg?dl^?1(sub-diabetic) and 150–200 mg?dl^?1(mild diabetic) were selected for the short term antidiabetic studies and severely diabetic rats (FBG?>?300 mg?dl^?1) were chosen for the long term antidiabetic and hypolipemic studies of PC seed extract. Laser induced breakdown spectroscopy (LIBS) was used to detect trace elements in the PC extract and the intensity ratios of trace elements were estimated. The dose of 250 mg?kg^?1 of PC extract was found to be the most effective in lowering blood glucose level (BGL) of normal, sub, mild and severely diabetic rats during FBG and glucose tolerance test (GTT) studies. Lipid profile studies on severely diabetic rats showed substantial reduction in total cholesterol, triglycerides, very low density lipoprotein, and low density lipoprotein and an increase in the total protein, body weight, high density lipoprotein, and hemoglobin after 28 days of treatment. Significant reduction in urine sugar and protein levels was also observed. LIBS analysis of the PC extract revealed the presence of Mg, Si, Na, K, Ca, Zn and Cl. The study validates the traditional use of PC in the treatment of diabetes and confirms its antilipemic potential. The antidiabetic activity of PC extract may partly be due to the presence of appreciable amounts of insulin potentiating elements like Mg, Ca, and K.     

Metabolic profiling in human lung injuries by high-resolution nuclear magnetic resonance spectroscopy of bronchoalveolar lavage fluid (BALF)

We present a method for identifying biomarkers in human lung injury. The method is based on high-resolution nuclear magnetic resonance (NMR) spectroscopy applied to bronchoalveolar lavage fluid (BALF) collected from lungs of critically ill patients. This biological fluid can be obtained by bronchoscopic and non-bronchoscopic methods. The type of lung injury in acute respiratory failure presenting as acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), continues to challenge critical care physicians. We characterize different metabolites in BAL fluid by non-bronchoscopic method (mBALF) for better diagnosis and understanding of ALI/ARDS by NMR spectroscopy. NMR spectra of mBALF collected from 30 patients (9 controls, 10 ARDS and 11 ALI) were analyzed for the identification of biomarkers. Statistical methods such as principal components analysis and partial least square discriminant analysis were carried out on ¹H NMR spectrum of mBALF to identify biomarker responsible for separation among different lung injuries classes (ALI and ARDS) and normal lungs. The corresponding correlation of biomarkers with metabolic cycle has given insight into metabolism of lung injuries in critically ill patients. Our study shows statistically significant differentiation of various metabolites concentration in mBALF collected from lungs of ALI, ARDS and healthy control patients, making NMR spectroscopy as a possible new method of characterizing human lung injury.     

In vitro antioxidant and antibacterial properties of hydrolysed proteins of delimed tannery fleshings: comparison of acid hydrolysis and fermentation methods

Proteins in delimed tannery fleshings were fermentatively hydrolysed using Enterococcus faecium NCIM5335 and also hydrolysed using mild organic acids (formic acid and propionic acid). The liquor portion containing hydrolysed proteins was spray dried, in both the cases, to obtain a powder. The spray dried powder was evaluated for in vitro antioxidant activities with respect to scavenging different free radicals and antibacterial properties against nine different pathogens. Fermentation and acid hydrolysates scavenged 83 and 75.3% of 2,2-azino-bis-3-ethyl-benzthiazoline-6-sulphonic acid (ABTS) radicals, respectively, at a protein concentration of 0.25 mg. Further, fermentation hydrolysate showed higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of 59% as compared to 56% scavenging by acid hydrolysate at a protein concentration of 5 mg. Acid hydrolysate exhibited lesser (82.3%) peroxy radical scavenging compared to hydrolysate from fermentation (88.2%) at a protein concentration of 10 mg. However, acid hydrolysate exhibited higher (89.2%) superoxide anion scavenging while its fermentation counterpart showed lower activity (85.4%) at 2.5 mg hydrolysate protein. Well as superoxide anion scavenging properties. All the in vitro antioxidant properties exhibited dose dependency. Fermentation hydrolysate exhibited maximum antagonistic activity against Salmonella typhi FB231, from among host of pathogens evaluated. Both the hydrolysates have potential to be ingredients in animal feeds and can help reduce oxidative stress in the animals.     

Sustainability and cyanobacteria (blue-green algae): facts and challenges

Cyanobacteria (blue-green algae) are widely distributed Gram-negative oxygenic photosynthetic prokaryotes with a long evolutionary history. They have potential applications such as nutrition (food supplements and fine chemicals), in agriculture (as biofertilizer and in reclamation of saline USAR soils) and in wastewater treatment (production of exopolysaccharides and flocculants). In addition, they also produce wide variety of chemicals not needed for their normal growth (secondary metabolites) which show powerful biological activities such as strong antiviral, antibacterial, antifungal, antimalarial, antitumoral and anti-inflammatory activities useful for therapeutic purposes. In recent years, cyanobacteria have gained interest for producing biofuels (both biomass and H₂ production). Because of their simple growth needs, it is potentially cost-effective to exploit cyanobacteria for the production of recombinant compounds of medicinal and commercial value. Recent advances in culture, screening and genetic engineering techniques have opened new ways to exploit the potential of cyanobacteria. This review analyses the sustainability of cyanobacteria to solve global problems such as food, energy and environmental degradation. It emphasizes the need to adopt multidisciplinary approaches and a multi-product production (biorefinery) strategy to harness the maximum benefit of cyanobacteria.     

Synthesis, crystal structure, and in vitro biological evaluation of C-6 pyrimidine derivatives: new lead structures for monitoring gene expression in vivo

Novel C-6 substituted pyrimidine derivatives are good substrates of herpes simplex virus type 1 thymidine kinase (HSV1-TK). Enzyme kinetic experiments showed that our lead compound, N-methyl DHBT (N-methyl-6-(1,3-dihydroxyisobutyl) thymine; N-Me DHBT), is phosphorylated at a similar rate compared to "gold standard" 9-[4-fluoro-3-(hydroxymethyl)butyl]guanine, FHBG, (K(m) = 10 ± 0.3 μM; k(cat) = 0.036 ± 0.015 sec(-1)). Additionally, it does not show cytotoxic properties on B16F1 cells up to a concentration of 10 mM. The x-ray analysis of the crystal structures of HSV1-TK with N-Me DHBT and of HSV1-TK with the fluorinated derivative N-Me FHBT confirmed the binding mode predicted by docking studies and their substrate characteristics. Moreover, the crystal structure of HSV1-TK with N-Me DHBT revealed an additional water-mediated H-bond interesting for the design of further analogues.     

Molecular characterization of lapinized classical Swine Fever vaccine strain by full-length genome sequencing and analysis

The complete genome of a lapinized classical swine fever virus (CSFV) vaccine strain was amplified into nine overlapping fragments by RT-PCR, and nucleotide sequences were determined. Complete genome sequence alignment and phylogenetic analysis indicated 92.6-98.6% identities at the nucleotide level with other reported CSFV strains and could be grouped into subgroup 1.1 along with other attenuated strains of CSFV. The 5'-UTR demonstrated >97.0% nucleotide similarity with most of vaccine CSFV strains from China. Further, its 3'-UTR sequence indicated a length similar to all the CSFV strains from China with >98.0% nucleotide similarity, although high length heterogeneity of 3'-UTR was reported among different CSFV strains. There was 12 nt (TTTTCTTTTTTT) insertion in 3'-UTR similar to other reported attenuated vaccine strains. However, secondary structure of 3'-UTR indicated that Indian CSFV strain requires further passage to obtain a 3'-UTR structure similar to most of the attenuated strains.     

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation,differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection.     

Treatment with 17-allylamino-17-demethoxygeldanamycin ameliorated symptoms of Bartter syndrome type IV caused by mutated Bsnd in mice

Mutations of BSND, which encodes barttin, cause Bartter syndrome type IV. This disease is characterized by salt and fluid loss, hypokalemia, metabolic alkalosis, and sensorineural hearing impairment. Barttin is the β-subunit of the ClC-K chloride channel, which recruits it to the plasma membranes, and the ClC-K/barttin complex contributes to transepithelial chloride transport in the kidney and inner ear. The retention of mutant forms of barttin in the endoplasmic reticulum (ER) is etiologically linked to Bartter syndrome type IV. Here, we report that treatment with 17-allylamino-17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor, enhanced the plasma membrane expression of mutant barttins (R8L and G47R) in Madin–Darby canine kidney cells. Administration of 17-AAG to Bsnd^R8L/R8L knock-in mice elevated the plasma membrane expression of R8L in the kidney and inner ear, thereby mitigating hypokalemia, metabolic alkalosis, and hearing loss. These results suggest that drugs that rescue ER-retained mutant barttin may be useful for treating patients with Bartter syndrome type IV.     

Purification and chemical characterization of antimicrobial compounds from a new soil isolate Streptomyces rimosus MTCC 10792

A new isolate of Streptomyces sp. from soil of state Chhattisgarh (India) having broad spectrum antibacterial and antifungal activity was obtained. The active strain was identified as Streptomyces rimosus subsp. rimosus with accession number MTCC 10792 based on physiological, biochemical characteristics and 16S rRNA sequence homology studies. Antimicrobial compound produced by S. rimosus was tested against the drug resistance pathogens by the Bauer and Kirby method. The crude active metabolite was extracted using solvent n-butanol and purified by silica column chromatography and HPLC method. The physicochemical characteristics of the one purified compound viz. color, melting point, solubility, elemental analysis, ESIMS, IR, UV, 1HNMR, ¹³CNMR and chemical reactions have been investigated. Purified antimicrobial compound produced by S. rimosus MTCC 10792 at concentration 25 μg/mL showed antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium tuberculosis H37R as well as broad activity against all tested bacterial and fungal pathogens.