A short review on creatine–creatine kinase system in relation to cancer and some experimental results on creatine as adjuvant in cancer therapy

The creatine/creatine kinase (CK) system plays a key role in cellular energy buffering and transport. In vertebrates, CK has four isoforms expressed in a tissue-specific manner. In the process of creatine biosynthesis several other important metabolites are formed. The anticancer effect of creatine had been reported in the past, and recent literature has reported low creatine content in several types of malignant cells. Furthermore, creatine can protect cardiac mitochondria from the deleterious effects of some anticancer compounds. Previous work from our laboratory showed progressive decrease of phosphocreatine, creatine and CK upon transformation of skeletal muscle into sarcoma. It was convincingly demonstrated that prominent expression of creatine-synthesizing enzymes l-arginine: glycine amidinotransferase and N-guanidinoacetate methyltransferase occurs in sarcoma, Ehrlich ascites carcinoma and sarcoma 180 cells; whereas, both these enzymes are virtually undetectable in skeletal muscle. Creatine transporter also remained unaltered in malignant cells. The anticancer effect of methylglyoxal had been known for a long time. The present work shows that this anticancer effect of methylglyoxal is significantly augmented in presence of creatine. On creatine supplementation the effect of methylglyoxal plus ascorbic acid was further augmented and there was no visible sign of tumor. Moreover, creatine and CK, which were very low in sarcoma tissue, were significantly elevated with the concomitant regression of tumor.     

Effects of essential oils on methane production and fermentation by, and abundance and diversity of, rumen microbial populations

Five essential oils (EOs), namely, clove oil (CLO), eucalyptus oil (EUO), garlic oil (GAO), origanum oil (ORO), and peppermint oil (PEO), were tested in vitro at 3 different doses (0.25, 0.50, and 1.0 g/liter) for their effect on methane production, fermentation, and select groups of ruminal microbes, including total bacteria, cellulolytic bacteria, archaea, and protozoa. All the EOs significantly reduced methane production with increasing doses, with reductions by 34.4%, 17.6%, 42.3%, 87%, and 25.7% for CLO, EUO, GAO, ORO, and PEO, respectively, at 1.0 g/liter compared with the control. However, apparent degradability of dry matter and neutral detergent fiber also decreased linearly with increasing doses by all EOs except GAO. The concentrations of total volatile fatty acids were not affected by GAO, EUO, or PEO but altered linearly and quadratically by CLO and ORO, respectively. All the EOs also differed in altering the molar proportions of acetate, propionate, and butyrate. As determined by quantitative real-time PCR, all the EOs decreased the abundance of archaea, protozoa, and major cellulolytic bacteria (i.e., Fibrobacter succinogenes, Ruminococcus flavefaciens, and R. albus) linearly with increasing EO doses. On the basis of denaturing gradient gel electrophoresis analysis, different EOs changed the composition of both archaeal and bacterial communities to different extents. The Shannon-Wiener diversity index (H') was reduced for archaea by all EOs in a dose-dependent manner but increased for bacteria at low and medium doses (0.25 and 0.50 g/liter) for all EOs except ORO. Due to the adverse effects on feed digestion and fermentation at high doses, a single EO may not effectively and practically mitigate methane emission from ruminants unless used at low doses in combinations with other antimethanogenic compounds.     

Proteomic analysis and antivenomics study of Western India Naja naja venom: correlation between venom composition and clinical manifestations of cobra bite in this region

Background: Snakebite is a severe problem in the tropical countries including Indian subcontinent. Premier cases of cobra bites are being reported from western India (WI).

Research design and methods: The proteome of WI N. naja venom (NnV) was deciphered by high resolution mass spectrometry analysis of venom, further fractionated by gel filtration (GF) or RP-HPLC followed by SDS-PAGE and then tandem mass spectrometric analysis of protein bands. The efficacy of commercial polyantivenom (PAV) towards WINnV was assessed by ELISA, immuno-blot, neutralization, and venom-PAV immunoaffinity chromatography studies.

Results: Proteomic analysis of WINnV, GF fractions, and SDS-PAGE protein bands of RP-HPLC and GF peaks identified 14, 34, 40, and 54, distinct proteins, respectively, when searched against Elapidae database. The biochemical properties of WINnV correlated well with its proteome composition and pathophysiology of cobra envenomation, including neuroparalysis. This study also highlighted the differences in proteome composition between WINnV and previously reported Eastern India NnV. The tested antivenoms exhibited poor immuno-recognition and neutralization of low molecular mass proteins (<20 kDa), such as three-finger toxins, the major class of protein in WINnV.

Conclusion: Improvements in production protocols of antivenoms is the necessity of the hour, supplemented with antibodies raised against the poorly recognized toxins.     

hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids

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Identification of a molecular marker for genotyping human lymphatic filarial nematode parasite Wuchereria bancrofti

In India, Mass Drug Administration is on going towards elimination of lymphatic filariasis in many areas, which might lead to intense selection pressure on the parasite populations and their genetic restructuring. This calls for molecular finger printing of Wuchereria bancrofti parasite populations at national level and monitoring genetic changes in the future. For this purpose a reliable, less expensive, rapid, and reproducible molecular tool is necessary, which is not available for W. bancrofti at this time. We identified robust molecular markers based on the comparison of random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP) profiles and the genetic data generated from parasite populations collected from areas in Northern (Varanasi, Uttar Pradesh state), Southern (Kozhikode, Kerala State) and Central regions (Jagdalpur, Chattisgarh state) of India, where lymphatic filariasis is endemic for many decades. RAPD profiles for these parasite populations were generated using three different primers and the dendrograms constructed using the profiles were all different. In order to identify appropriate RAPD primer(s), we compared the results of RAPD with the fingerprint profile and genetic data obtained by the more reliable AFLP technique, using the parasite populations from the same areas. RAPD marker (OP8) primer produced phylogenetic data almost similar to that of AFLP analysis. The marker was able to reveal variations between the parasite populations collected from Varanasi, Kozhikode, and Jagdalpur. Most importantly, RAPD primer OP8 produced reproducible results, when tested in three different trials. In view of the limited availability of W. bancrofti parasite DNA, along with a lower cost and ease of performance, RAPD appears to be more suitable compared to AFLP at the present juncture, since complete genome information of this parasite is still not available. Thus, RAPD primer OP8 can be a very useful molecular maker for DNA finger printing of W. bancrofti populations at present.     

Systematic Network and Meta-analysis on the Antiviral Mechanisms of Probiotics: A Preventive and Treatment Strategy to Mitigate SARS-CoV-2 Infection

Probiotics and Antimicrobial Proteins - With the alarming rise of infected cases and deaths, COVID-19 is a pandemic, affecting 220 countries worldwide. Until now, no specific treatment is available...     

Terpenoid indole alkaloid biosynthesis in Catharanthus roseus: effects and prospects of environmental factors in metabolic engineering

Biotechnology Letters - Plants synthesize a vast array of specialized metabolites that primarily contribute to their defense and survival under adverse conditions. Many of the specialized...     

Spiro Benzodiazepine Substituted Fluorocoumarins as Potent Anti-Anxiety Agents

Russian Journal of Bioorganic Chemistry - 1,5-Benzodiazepines are one of the important class of tranquilizers. The fusion of heterocyclic systems like coumarins and indolines with the...