Bacteria as a treasure house of secondary metabolites with anticancer potential.

Cancer stands in the frontline among leading killers worldwide and the annual mortality rate is expected to reach 16.4 million by 2040. Humans suffer from about 200 different types of cancers and many of them have a small number of approved therapeutic agents. Moreover, several types of major cancers are diagnosed at advanced stages as a result of which the existing therapies have limited efficacy against them and contribute to a dismal prognosis. Therefore, it is essential to develop novel potent anticancer agents to counteract cancer-driven lethality. Natural sources such as bacteria, plants, fungi, and marine microorganisms have been serving as an inexhaustible source of anticancer agents. Notably, over 13,000 natural compounds endowed with different pharmacological properties have been isolated from different bacterial sources. In the present article, we have discussed about the importance of natural products, with special emphasis on bacterial metabolites for cancer therapy. Subsequently, we have comprehensively discussed the various sources, mechanisms of action, toxicity issues, and off-target effects of clinically used anticancer drugs (such as actinomycin D, bleomycin, carfilzomib, doxorubicin, ixabepilone, mitomycin C, pentostatin, rapalogs, and romidepsin) that have been derived from different bacteria. Furthermore, we have also discussed some of the major secondary metabolites (antimycins, chartreusin, elsamicins, geldanamycin, monensin, plicamycin, prodigiosin, rebeccamycin, salinomycin, and salinosporamide) that are currently in the clinical trials or which have demonstrated potent anticancer activity in preclinical models. Besides, we have elaborated on the application of metagenomics in drug discovery and briefly described about anticancer agents (bryostatin 1 and ET-743) identified through the metagenomics approach.

UPLC-ESI MS/MS- and GC-MS-Based Altitudinal Variations in the Bioactive Potential of Mikania micrantha and Ageratum houstonianum.

Traditional medicinal plants have attracted scientific interest due to their bioactive compounds, and the levels of their constituents vary with location and altitude. The present study was designed to evaluate the pharmacological potential of two selected traditional medicinal plants, Mikania micrantha and Ageratum houstonianum collected from two sites, Murlen National Park (MNP) and Dampa Tiger Reserve (DTR), located at different altitudes. Both plant species are used by local traditional healers in Mizoram, Northeast India, to treat various health problems. We hypothesized that altitudinal variation would affect these plants' chemical composition and bioactive potential. Plant extracts were evaluated for antioxidant and cytotoxic activities. The results show that the plants located at a higher altitude, i.e., MNP, showed higher TPC (615.7 ± 0.58 and 453.80 ± 0.95 µg gallic acid equivalents/mg of plant extract dry weight (µg GAE/mg) for M. micrantha and A. houstonianum , respectively) and TFC (135.4 ± 0.46 and 120.66 ± 1.93 µg quercetin equivalents/mg of plant extract dry weight (µg GE/mg) for M. micrantha and A. houstonianum, respectively). The extract of A. houstonianum. (MNP) exhibited significantly greater antioxidant activity against ABTS radicals (IC50 241.6 µg/mL) as compared to the extract of A. houstonianum (DTR) (IC50 371.2 µg/mL). The composition of the bioactive compounds present in the plants was determined using UPLC-ESI MS/MS and GC/MS, which detected five and ten compounds in the A. houstonianum and M. micrantha extracts, respectively. Plant species collected from the Murlen National Park site had high bioactivity potential and contained several bioactive compounds. A distinct variation between the volatile and non-volatile compounds was revealed. The collective data in this study show the influence of altitude on the biological compound production of selected medicinal plants. The findings will be utilized in the plant material needed for developing bioactive formulations.

Escaping mechanisms of ESKAPE pathogens from antibiotics and their targeting by natural compounds.

The microorganisms that have developed resistance to available therapeutic agents are threatening the globe and multidrug resistance among the bacterial pathogens is becoming a major concern of public health worldwide. Bacteria develop protective mechanisms to counteract the deleterious effects of antibiotics, which may eventually result in loss of growth-inhibitory potential of antibiotics. ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens display multidrug resistance and virulence through various mechanisms and it is the need of the hour to discover or design new antibiotics against ESKAPE pathogens. In this article, we have discussed the mechanisms acquired by ESKAPE pathogens to counteract the effect of antibiotics and elaborated on recently discovered secondary metabolites derived from bacteria and plant sources that are endowed with good antibacterial activity towards pathogenic bacteria in general, ESKAPE organisms in particular. Abyssomicin C, allicin, anthracimycin, berberine, biochanin A, caffeic acid, daptomycin, kibdelomycin, piperine, platensimycin, plazomicin, taxifolin, teixobactin, and thymol are the major metabolites whose antibacterial potential have been discussed in this article.

Paradoxical functions of long noncoding RNAs in modulating STAT3 signaling pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the lethal and leading types of cancer threatening the globe with a high mortality rate. STAT3 is an oncogenic transcription factor that is aberrantly activated in several human malignancies including HCC. Many STAT3-driven genes control cell proliferation and survival, apoptotic resistance, cell cycle progression, metastasis, and chemotherapeutic resistance. STAT3 signaling is regulated by endogenous modulators such as protein tyrosine phosphatase (PTP), suppressor of cytokine signaling (SOCS), protein inhibitor of activated STAT (PIAS), and various long noncoding RNAs (lncRNAs). Interestingly, lncRNAs have been reported to exhibit oncogenic and tumor suppressor functions, and these effects are mediated through diverse molecular mechanisms including sponging of microRNAs (miRs), transcription activation/inhibition, and epigenetic modifications. In this article, we have discussed the possible role of STAT3 signaling in hepatocarcinogenesis and various mechanisms by which lncRNAs impart their oncogenic or tumor suppressive action by modulating the STAT3 pathway in HCC.

Minimizing hazardous impact of food waste in a circular economy - Advances in resource recovery through green strategies.

Recent trends in food waste and its management have increasingly started to focus on treating it as a reusable resource. The hazardous impact of food waste such as the release of greenhouse gases, deterioration of water quality and contamination of land areas are a major threat posed by food waste. Under the circular economy principles, food waste can be used as a sustainable supply of high-value energy, fuel, and nutrients through green techniques such as anaerobic digestion, co-digestion, composting, enzymatic treatment, ultrasonic, hydrothermal carbonization. Recent advances made in anaerobic co-digestion are helping in tackling dual or even multiple waste streams at once with better product yields. Integrated approaches that employ pre-processing the food waste to remove obstacles such as volatile fractions, oils and other inhibitory components from the feedstock to enhance their bioconversion to reduce sugars. Research efforts are also progressing in optimizing the operational parameters such as temperature, pressure, pH and residence time to enhance further the output of products such as methane, hydrogen and other platform chemicals such as lactic acid, succinic acid and formic acid. This review brings together some of the recent progress made in the green strategies towards food waste valorization.

Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds.

Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhanced metastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies.

Friends or foes? Emerging insights from fungal interactions with plants.

Fungi interact with plants in various ways, with each interaction giving rise to different alterations in both partners. While fungal pathogens have detrimental effects on plant physiology, mutualistic fungi augment host defence responses to pathogens and/or improve plant nutrient uptake. Tropic growth towards plant roots or stomata, mediated by chemical and topographical signals, has been described for several fungi, with evidence of species-specific signals and sensing mechanisms. Fungal partners secrete bioactive molecules such as small peptide effectors, enzymes and secondary metabolites which facilitate colonization and contribute to both symbiotic and pathogenic relationships. There has been tremendous advancement in fungal molecular biology, omics sciences and microscopy in recent years, opening up new possibilities for the identification of key molecular mechanisms in plant-fungal interactions, the power of which is often borne out in their combination. Our fragmentary knowledge on the interactions between plants and fungi must be made whole to understand the potential of fungi in preventing plant diseases, improving plant productivity and understanding ecosystem stability. Here, we review innovative methods and the associated new insights into plant-fungal interactions.