Repurposing of clinically proven bioactive compounds for targeted treatment of Alzheimer's disease using molecular docking approach.

Neurodegenerative diseases like Alzheimer's have become a growing concern as it is difficult to cure. Tau protein is found to be playing a major role in Alzheimer's disease, and the majority of drugs that are currently on the market are not only prohibitively expensive but also come packaged with side effects that the body cannot tolerate. Repurposing existing compounds is a successful and optimistic strategy that offers reduced risk and increased possibility. We aim to retrieve the existing drugs and analyze them using in-silico techniques. We have retrieved the compounds from the Selleckchem natural product library, and the ability of the drug to cross Blood Brain Barrier (BBB) and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties were examined using SwissADME. The structure of Tau protein (2MZ7) was then retrieved from PDB, and molecular docking of the compounds was performed using the PyRx-Virtual Screening Tool. Initially, 92 compounds passed the ADMET screening criteria, out of which the compound Ligustroflavone was found to have the most favourable binding affinity without violating Lipinski's rule of 5 of the compounds in the library.

Nanovesicle and extracellular polymeric substance synthesis from the remediation of heavy metal ions from soil.

Heavy metal toxicity affects aquatic plants and animals, disturbing biodiversity and ecological balance causing bioaccumulation of heavy metals. Industrialization and urbanization are inevitable in modern-day life, and control and detoxification methods need to be accorded to meet the hazardous environment. Microorganisms and plants have been widely used in the bioremediation of heavy metals. Sporosarcina pasteurii, a gram-positive bacterium that is widely known for its calcite precipitation property in bio-cementing applications has been explored in the study for its metal tolerance ability for the first time. S. pasteurii SRMNP1 (KF214757) can tolerate silver stress to form nanoparticles and can remediate multiple heavy metals to promote the growth of various plants. This astounding property of the isolate warranted extensive examinations to comprehend the physiological changes during an external heavy metal stress condition. The present study aimed to understand various physiological responses occurring in S. pasteuriiSRMNP1 during the metal tolerance phenomenon using electron microscopy. The isolate was subjected to heavy metal stress, and a transmission electron microscope examination was used to analyze the physiological changes in bacteria to evade the metal stress. S. pasteurii SRMNP1 was tolerant against a wide range of heavy metal ions and can withstand a broad pH range (5-9). Transmission Electron Microscopy (TEM) examination of S. pasteurii SRMNP1 followed by 5 mM nickel sulfate treatment revealed the presence of nanovesicles encapsulating nanosized particles in intra and extracellular spaces. This suggests that the bacteria evade the metal stress by converting the metal ions into nanosized particles and encapsulating them within nanovesicles to efflux them through the vesicle budding mechanism. Moreover, the TEM images revealed an excessive secretion of extracellular polymeric substances by the strain to discharge the metal particles outside the bacterial system. S. pasteurii can be foreseen as an effective bioremediation agent with the potential to produce nanosized particles, nanovesicles, and extracellular polymeric substances. This study provides physiological evidence that, besides calcium precipitation applications, S. pasteurii can further be explored for its multidimensional roles in the fields of drug delivery and environmental engineering.

Implications of reactive oxygen species in lung cancer and exploiting it for therapeutic interventions.

Lung cancer is the second (11.4%) most commonly diagnosed cancer and the first (18%) to cause cancer-related deaths worldwide. The incidence of lung cancer varies significantly among men, women, and high and low-middle-income countries. Air pollution, inhalable agents, and tobacco smoking are a few of the critical factors that determine lung cancer incidence and mortality worldwide. Reactive oxygen species are known factors of lung carcinogenesis resulting from the xenobiotics and their mechanistic paths are under critical investigation. Reactive oxygen species exhibit dual roles in cells, as a tumorigenic and anti-proliferative factor, depending on spatiotemporal context. During the precancerous state, ROS promotes cancer origination through oxidative stress and base-pair substitution mutations in pro-oncogenes and tumor suppressor genes. At later stages of tumor progression, they help the cancer cells in invasion, and metastases by activating the NF-kB and MAPK pathways. However, at advanced stages, when ROS exceeds the threshold, it promotes cell cycle arrest and induces apoptosis in cancer cells. ROS activates extrinsic apoptosis through death receptors and intrinsic apoptosis through mitochondrial pathways. Moreover, ROS upregulates the expression of beclin-1 which is a critical component to initiate autophagy, another form of programmed cell death. ROS is additionally involved in an intermediatory step in necroptosis, which catalyzes and accelerates this form of cell death. Various therapeutic interventions have been attempted to exploit this cytotoxic potential of ROS to treat different cancers. Growing body of evidence suggests that ROS is also associated with chemoresistance and cancer cell immunity. Considering the multiple roles of ROS, this review highlights the exploitation of ROS for various therapeutic interventions. However, there are still gaps in the literature on the dual roles of ROS and the involvement of ROS in cancer cell immunity and therapy resistance.

Emerging priorities for microbial metagenome research.

Overwhelming anthropogenic activities lead to deterioration of natural resources and the environment. The microorganisms are considered desirable, due to their suitability for easy genetic manipulation and handling. With the aid of modern biotechnological techniques, the culturable microorganisms have been widely exploited for the benefit of mankind. Metagenomics, a powerful tool to access the abundant biodiversity of the environmental samples including the unculturable microbes, to determine microbial diversity and population structure, their ecological roles and expose novel genes of interest. This review focuses on the microbial adaptations to the adverse environmental conditions, metagenomic techniques employed towards microbial biotechnology. Metagenomic approach helps to understand microbial ecology and to identify useful microbial derivatives like antibiotics, toxins, and enzymes with diverse and enhanced function. It also summarizes the application of metagenomics in clinical diagnosis, improving microbial ecology, therapeutics, xenobiotic degradation and impact on agricultural crops.