Sodium Butyrate Ameliorates l‐Arginine‐Induced Pancreatitis and Associated Fibrosis in Wistar Rat: Role of Inflammation and Nitrosative Stress

Several reports indicated that histone deacetylases (HDACs) play a crucial role in inflammation and fibrogenesis. Sodium butyrate (SB) is a short‐chain fatty acid having HDAC inhibition potential. The present study aimed to evaluate the protective effect of SB against l ‐arginine (l ‐Arg)‐induced pancreatic fibrosis in Wistar rats. Pancreatic fibrosis was induced by twice intraperitoneal (i.p.) injections of 20% l ‐Arg (250 mg/100 g) at 2‐h interval on day 1, 4, 7, and 10, whereas SB (800 mg/kg/day) was administrated for 10 days. At the end of the study, biochemical estimations, histological alterations, DNA damage, and the expression of various proteins were evaluated. Posttreatment of SB decreased l ‐Arg‐induced oxidative and nitrosative stress, DNA damage, histological alterations, and fibrosis. Interestingly, posttreatment of SB significantly decreased the expression of α‐smooth muscle actin, interleukin‐1β, inducible nitric oxide synthase, and 3‐nitrotyrosine. The present study demonstrated that posttreatment of SB alleviates l ‐Arg‐induced pancreatic damage and fibrosis in rat.     

The antimicrobial activity of the appetite peptide hormone ghrelin

The present study examined the antimicrobial activity of the peptide ghrelin. Both major forms of ghrelin, acylated ghrelin (AG) and desacylated ghrelin (DAG), demonstrated the same degree of bactericidal activity against Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa), while bactericidal effects against Gram-positive Staphylococcus aureus (S. aureus) and Enterococcus faecalis (E. faecalis) were minimal or absent, respectively. To elucidate the bactericidal mechanism of AG and DAG against bacteria, we monitored the effect of the cationic peptides on the zeta potential of E. coli. Our results show that AG and DAG similarly quenched the negative surface charge of E. coli, suggesting that ghrelin-mediated bactericidal effects are influenced by charge-dependent binding and not by acyl modification. Like most cationic antimicrobial peptides (CAMPs), we also found that the antibacterial activity of AG was attenuated in physiological NaCl concentration (150mM). Nonetheless, these findings indicate that both AG and DAG can act as CAMPs against Gram-negative bacteria.     

The classical nuclear localization signal receptor, importin-alpha, is required for efficient transition through the G1/S stage of the cell cycle in Saccharomyces cerevisiae

There is significant evidence linking nucleocytoplasmic transport to cell cycle control. The budding yeast, Saccharomyces cerevisiae, serves as an ideal model system for studying transport events critical to cell cycle progression because the nuclear envelope remains intact throughout the cell cycle. Previous studies linked the classical nuclear localization signal (cNLS) receptor, importin-alpha/Srp1, to the G(2)/M transition of the cell cycle. Here, we utilize two engineered mutants of importin-alpha/Srp1 with specific molecular defects to explore how protein import affects cell cycle progression. One mutant, Srp1-E402Q, is defective in binding to cNLS cargoes that contain two clusters of basic residues termed a bipartite cNLS. The other mutant, Srp1-55, has defects in release of cNLS cargoes into the nucleus. Consistent with distinct in vivo functional consequences for each of the Srp1 mutants analyzed, we find that overexpression of different nuclear transport factors can suppress the temperature-sensitive growth defects of each mutant. Studies aimed at understanding how each of these mutants affects cell cycle progression reveal a profound defect at the G(1) to S phase transition in both srp1-E402Q and srp1-55 mutants as well as a modest G(1)/S defect in the temperature-sensitive srp1-31 mutant, which was previously implicated in G(2)/M. We take advantage of the characterized defects in the srp1-E402Q and srp1-55 mutants to predict candidate cargo proteins likely to be affected in these mutants and provide evidence that three of these cargoes, Cdc45, Yox1, and Mcm10, are not efficiently localized to the nucleus in importin-alpha mutants. These results reveal that the classical nuclear protein import pathway makes important contributions to the G(1)/S cell cycle transition.     

Distinct cytokine profiles define clinical immune response to falciparum malaria in regions of high or low disease transmission

The immune effector response to Plasmodium falciparum infection involves a finely-tuned interplay between different cell types and cytokines. However, the processes by which they mediate the development of clinical immunity, in areas of different endemicity, are poorly understood. We analyzed circulating levels of pro-inflammatory (TNF, IFN-γ, IL-12, IL-16) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines in control and patient groups drawn from a P. falciparum-endemic and a non-endemic region of India. The endemic region control population exhibited a lower pro- to anti-inflammatory cytokine ratio, indicating a shift towards a high basal Th2 response. Levels of IL-10 contributed most towards the region-specific difference in basal cytokine response. IL-10 was also the strongest predictor of disease in the endemic region, while IL-12, along with IL-10 and IL-6, contributed most to disease outcome in the non-endemic region. A low, mean IFN-γ/IL-10 ratio was associated with disease severity in the endemic region (p < 0.0001). In contrast, a low mean IL-12/IL-10 ratio correlated with disease outcome in the non-endemic region (p < 0.0001). In the endemic region, IL-13 correlated negatively with IFN-γ in severe patients (Spearman's ρ: -0.49; p : 0.013), while in the non-endemic region, IL-13 correlated negatively with IL-6 in severe malaria patients (Spearman's ρ: -0.485; p : 0.001). In conclusion, levels of pro- and anti-inflammatory cytokines and the relative balance between the Th1 and Th2 response, illustrates how populations residing in areas of varying disease endemicity may respond to P. falciparum-induced immune challenge.     

Fungistatic activity of Semecarpus anacardium Linn. f nut extract

Alcoholic extract of dry nuts of S. anacardium showed dose dependent antifungal activity in vitro against Aspergillus fumigatus and Candida albicans. At 400 mg/ml concentration, growth of both the fungi was inhibited and considerable reduction in size of cells and hyphae was observed. Sporulation also decreased.     

In vitro antidiabetic,antioxidant, antimicrobial,and cytotoxic activity of Murraya koenigii leaf extract intercedes ZnO nanoparticles

Nanotechnology is an emerging field with tremendous potential and usage of medicinal plants and green preparation of nanoparticles (NPs) is one of the widely explored areas. These have been shown to be effective against different biological activities such as diabetes mellitus, cancer, antioxidant, antimicrobial, etc. The current studies focus on the green synthesis of zinc NPs (ZnO NPs) from aqueous leaf extract of Murraya koenigii (MK). The synthesized Murraya koeingii zinc oxide NPs (MK ZnO NPs) were characterized using UV–visible spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive spectrum (EDS) and cyclic voltammetry (CV). The synthesized MK ZnO NPs were evaluated for their in vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity. They demonstrated significant antidiabetic and cytotoxic activity, as well as moderate free-radical scavenging and antibacterial activity.     

Differences in the chemical constituents of Mangifera indica, infected with Aspergillus niger and Fusarium moniliformae

The isolation and characterization of the chemical constituents of different parts of Mangifera indica, sound and infected with two pathogenic fungi, viz. Aspergillus niger and Fusarium moniliformae, are described. Natural occurrence of two polyketideshikimate-derived depsides is reported for the first time. Additionally, a number of xanthones, flavonoids, triterpenes and amino acids, not encountered before in this species, are reported. The co-occurrence of mangiferin, 1,3,6,7-tetra- and 1,3,5,6,7-pentaoxygenated xanthones and the quantitative variation of the latter two compounds with the growing of the plant and during the fungal infection are biochemically significant. The protector role of the flavonoids and other C₁₅ metabolites to M. indica from the ingress of the fungal hyphae is indicated. The two pathogenic fungi secreted a number of mycotoxins in different parts of the host species during its vegetation and flowering periods. During the elaboration of these toxic metabolites, the host-pathogen interaction played an important role. Evidence is presented for A. niger as a mycotoxin producing fungus.     

Characterizing the chemical complexity of patterned biomimetic membranes

Biomembranes are complex, heterogeneous, dynamic systems playing essential roles in numerous processes such as cell signaling and membrane trafficking. Model membranes provide simpler platforms for studying biomembrane dynamics under well-controlled environments. Here we present a modified polymer lift-off approach to introduce chemical complexity into biomimetic membranes by constructing domains of one lipid composition (here, didodecylphosphatidylcholine) that are surrounded by a different lipid composition (e.g., dipentadecylphosphatidylcholine), which we refer to as patterned backfilled samples. Fluorescence microscopy and correlation spectroscopy were used to characterize this patterning approach. We observe two types of domain populations: one with diffuse boundaries and a minor fraction with sharp edges. Lipids within the diffuse domains in patterned backfilled samples undergo anomalous diffusion, which results from nonideally mixed clusters of gel phase lipid within the fluid domains. No lateral diffusion was observed within the minor population of domains with well-defined borders. These results suggest that, while membrane patterning by a variety of approaches is useful for biophysical and biosensor applications, a thorough and systematic characterization of the resulting biomimetic membrane, and its unpatterned counterpart, is essential.     

Steviol glycoside accumulation and expression profiling of biosynthetic pathway genes in elicited in vitro cultures of Stevia rebaudiana

In Vitro Cellular & Developmental Biology - Plant - In the present study, different elicitors, viz., polyethylene glycol (PEG), alginate (ALG), chitosan (CHI), salicylic acid (SA), and yeast...     

Single cell-level detection and quantitation of leaky protein expression from any strongly regulated bacterial system

Extremely low levels of “leaky” expression of genes in bacterial protein expression systems can severely curtail cell viability when expressed proteins are toxic. A general method for sensitive detection of such expression is lacking. Here, we present a method based on microscopic visualization of a fluorescent “reporter” protein (RFP–HU-A) constructed by fusing red fluorescent protein (RFP) to the N-terminus of a nucleoid-associated, histone-like DNA-binding protein, HU-A. Localization of RFP–HU-A within nucleoids facilitates detection, quantitation, and characterization of leaky expression at the single-cell level.