Contrasting roles for G-quadruplexes in regulating human Bcl-2 and virus homologues KSHV KS-Bcl-2 and EBV BHRF1.

Herpesviruses are known to acquire several genes from their hosts during evolution. We found that a significant proportion of virus homologues encoded by HSV-1, HSV-2, EBV and KSHV and their human counterparts contain G-quadruplex motifs in their promoters. We sought to understand the role of G-quadruplexes in the regulatory regions of viral Bcl-2 homologues encoded by KSHV (KS-Bcl-2) and EBV (BHRF1). We demonstrate that the KSHV KS-Bcl-2 and the EBV BHRF1 promoter G-quadruplex motifs (KSHV-GQ and EBV-GQ) form stable intramolecular G-quadruplexes. Ligand-mediated stabilization of KS-Bcl-2 and BHRF1 promoter G-quadruplexes significantly increased the promoter activity resulting in enhanced transcription of these viral Bcl-2 homologues. Mutations disrupting KSHV-GQ and EBV-GQ inhibit promoter activity and render the KS-Bcl-2 and the BHRF1 promoters non-responsive to G-quadruplex ligand. In contrast, promoter G-quadruplexes of human bcl-2 gene inhibit promoter activity. Further, KS-Bcl-2 and BHRF1 promoter G-quadruplexes augment RTA (a virus-encoded transcription factor)-mediated increase in viral bcl-2 promoter activity. In sum, this work highlights how human herpesviruses have evolved to exploit promoter G-quadruplexes to regulate virus homologues to counter their cellular counterparts.

KLa(0.95-x)GdxF4:Eu3+ hexagonal phase nanoparticles as luminescent probes for in vitro Huh-7 cancer cell imaging.

A facile chemical route is reported for synthesizing red-emitting photoluminescent/MRI multi-functional KLa(0.95-x)GdxF4:Eu3+ (x = 0 to 0.4) bio-compatible nanomaterials for targeted in vitro tumor imaging. Hexagonal phase pure nanoparticles show a significant and systematic change in morphology with enhanced photoluminescence due to the substitution of La3+ with Gd3+ ions. Single phase ß-KLa(0.95-x)GdxF4:Eu3+ exhibits multifunctional properties, both intense red emission and strong paramagnetism for high-contrast bioimaging applications. These silica capped magnetic/luminescent nanoparticles show long-term colloidal stability, optical transparency in water, strong red emission, and low cytotoxicity. The cellular uptake of coated nanoparticles was investigated in liver cancer cell line Huh-7. Our findings suggest that these nanoparticles can serve as highly luminescent imaging probes for in vitro applications with potential for in vivo and live cell imaging applications.

Cancer Microbiome; Opportunities and Challenges.

BACKGROUND: Microbe-host association has emerged as a modulator in modern medicine. Cancer and its associated host microbes are collectively referred to as the cancer microbiome. The cancer microbiome is complex, and many aspects remain unclear including metabolic plasticity, microenvironment remodeling, cellular communications, and unique signatures within the host, all of which have a vital role in homeostasis and pathogenesis of host physiology. However, the role of the microbiome in cancer initiation, progression, and therapy is still poorly understood and remains to be explored. OBJECTIVE: The objective of this review is to elucidate the role of the microbiome in cancer metabolism and the tumor microenvironment. It also focuses on the importance of therapeutic opportunities and challenges in the manipulation of the cancer microbiome. METHODS: A literature search was conducted on the role of the microbiome in cancer initiation, progression, and therapy. CONCLUSION: The tumor microenvironment and cancer metabolism are significant in host-microbiome interactions. The microbiome can modulate standard cancer therapies like chemotherapy and immunotherapy. Microbiome transplantation has also been demonstrated as an effective therapy against cancer. Furthermore, the modulation of the microbiome also has potential clinical outcomes in modern medicine.

Nutrient profile of porridge made from Eleusine coracana (L.) grains: effect of germination and fermentation.

Porridge (koozh) is one of the traditional foods made from Eleusine coracana L. grains (Finger millet). It is a soft food prepared from processed (germinated & fermented) finger millet flour (FMF). However, in the modern world of fast food, koozh is usually prepared from non-processed (non-germinated & non-fermented) FMF. Hence, present study was undertaken to evaluate the macro and micro nutrient contents in koozh prepared from germinated (fermented & non-fermented) and non-germinated (fermented & non-fermented) FMF. Highest protein, carbohydrate and glycoprotein contents were found in koozh prepared from germinated & non-fermented FMF. The free amino acid contents are higher in germinated & fermented condition when compare to other preparations. No significant change was observed in the calorific value of all preparations. There is no statistical difference in macro-nutrients & micro-nutrients minerals such as calcium, iron, magnesium, manganese, phosphorous and zinc among all the preparations. However, copper content is higher in non-germinated condition, whereas selenium, silicon and sulphur are higher in germinated FMF when compared to others. Significant level of total phenol, total flavonoid and free radical scavenging activity was observed in all preparations, which increased further during fermentation. The present observations, lead us to conclude that koozh prepared from germinated & non-fermented FMF contains higher level of carbohydrate, protein and glycoprotein, however germinated & fermented koozh has increased aminoacids, phytochemicals and free radical scavenging activity. Hence it is suggested that the consumption of koozh made from germinated & fermented FMF may provide easily digestible and energetic nutrients for healthier life.

Synthesis and biological evaluation of isoindoloisoquinolinone, pyroloisoquinolinone and benzoquinazolinone derivatives as poly(ADP-ribose) polymerase-1 inhibitors.

A series of novel fused isoquinolinones with isoindoloisoquinolinone, pyroloisoquinolinone, and benzoquinalizinone skeletons were synthesized from corresponding phenethylimides. The isoquinolinone derivatives were evaluated for their protective effect on chicken erythrocytes subjected to oxidative damage. The effect of isoquinolinone derivatives were analysed by estimation of cell viability, antioxidant enzyme activities, DNA damage (comet assay), PARP-1 inhibition assay and molecular docking of the compounds with PARP-1 active site. The compounds CRR-271, CRR-288 and CRR-224+225 showed significant protective effect at 100 µM concentration. The PARP-1 inhibition assay revealed the IC50 values of CRR-271, CRR-288 and CRR-224+225 as <200 nM, further molecular docking studies shows higher binding energies with PARP-1 active site. Interesting findings in this study suggest that the novel isoquinolinone derivatives inhibit PARP-1 activity and protect cells against oxidative DNA damage, which could be implemented in the treatment of inflammatory diseases.

TNF-α suppression by glutathione preconditioning attenuates hepatic ischemia reperfusion injury in young and aged rats.

BACKGROUND AND AIM: Hepatic ischemia reperfusion (I/R) stimulates Kupffer cells and initiates injury through tumor necrosis factor-α (TNF-α) upregulation. Aim of this study was to compare the variable effects of reduced glutathione (GSH) pre-treatment on I/R liver injury in young and aged rats. METHODS: Wistar male rats were sorted into young (groups I-III) and aged (groups IV-VI). All groups except sham (groups I and IV) were subjected to 90-min ischemia and 2-h reperfusion. The treatment groups received 200 mg/kg bwt (groups III and VI) of GSH, 30 min prior to I/R. Variable effects of GSH were studied by transaminase activities, thiobarbituric acid-reactive substances (TBARS), GSH level, GSH/oxidized GSH (GSSG) ratio, TNF-α level, apoptotic markers and confirmed by histopathological observations. RESULTS: Our findings revealed that I/R inflicted more liver damage in aged rats than young rats. The GSH treatment prior to surgery significantly lowered the serum transaminase activities, hepatic TBARS level and effectively restored the GSH/GSSG ratio in both young and aged rats more remarkably in the mitochondria. Western analysis depicted that the GSH treatment effectively suppressed TNF-α expression and apoptotic markers in both young and aged rats. These findings were further confirmed by terminal deoxynucleotide transferase dUTP nick end labeling assay and histopathological observations of liver sections of young and aged rats. CONCLUSION: Restoration of GSH/GSSG ratio through GSH pre-conditioning inhibits TNF-α and apoptosis in hepatic I/R injury. Hence, GSH pre-conditioning may be utilized in both young and aged individuals during liver transplantation/surgery for better post-operative outcomes.