Efficacy of Andrographis paniculata against extended spectrum ß-lactamase (ESBL) producing E. coli.

BACKGROUND: A. paniculata is widely known for its medicinal values and is traditionally used to treat a wide range of diseases such as cancer, diabetes, skin infections, influenza, diarrhoea, etc. The phytochemical constituents of this plant possess unique and interesting biological activities. The main focus of this study was to evaluate the antibacterial property of crude ethyl acetate (CEA) extract of A. paniculata against E. coli clinical isolates along with molecular docking of 10 different bioactive components from this plant with CTX-M-15. METHODS: CEA extract was subjected to phytochemical and FTIR analysis. The E. coli isolates were tested for antibiotic susceptibility through disk-diffusion method to observe their resistance pattern towards different antibiotics. Antibacterial activity and biofilm assay were performed through broth microdilution using a 96-well microplate. CEA extract was further utilized to observe its effect on the expression of a gene encoding CTX-M-15. Finally, in-silico studies were performed where 10 different bioactive compounds from A. paniculata were molecularly docked with CTX-M-15. RESULTS: Phytochemical and FTIR analysis detected the presence of various secondary metabolites and functional groups in CEA extract respectively. Molecular docking provided the number of residues and bond lengths together with a positive docking score. Antibiotic susceptibility showed the multi-drug resistance of all the clinical strains of E. coli. The antibacterial and antibiofilm efficiency of CEA extract (25, 50 and 100 µg/ml) was tested and 100 µg/ml of the extract was more effective in all the strains of E. coli. All 3 ESBL producing strains of E. coli were subjected to gene expression analysis through PCR. Strains treated with 100 µg/ml of the extract showed a downregulation of the gene encoding CTX-M-15 compared to untreated controls. CONCLUSIONS: The utilization of CEA extract of A. paniculata proved an economical way of controlling the growth and biofilm formation of ESBL strains of E. coli. CEA extract was also able to downregulate the expression of a gene encoding CTX-M-15. Molecular docking of 10 different bioactive compounds from A. paniculata with CTX-M-15 provided the residues and bond lengths with a positive docking score.

Gelidiella acerosa inhibits lung cancer proliferation.

BACKGROUND: Lung adenocarcinoma is the most common subtype of Non small cell lung cancer in which the PI3K/Akt cascade is frequently deregulated. The ubiquitous expression of the PI3K and the frequent inactivation of PTEN accounts for the prolonged survival, evasion of apoptosis and metastasis in cancer. This has led to the development of PI3K inhibitors in the treatment of cancer. Synthetic PI3K inhibitors undergoing clinical and preclinical studies are toxic in animals. Hence, there is a critical need to identify PI3K inhibitor(s) of natural origin. The current study aims to explore the efficacy of the red algae Gelidiella acerosaon inhibition of cell proliferation, migration and the expression of cell survival genes in lung adenocarcinoma cell line A549. METHODS: The phytoconstituents of Gelidiella acerosa were extracted sequentially with solvents of different polarity, screened qualitatively and quantitatively for secondary metabolites and characterized by GC-MS. The in-vitro studies were performed to check the efficacy of the extract on cell proliferation (MTT assay), cell invasion (scratch assay and colony formation assay), apoptosis (fluorescent, confocal microscopy and flow cytometry) and expression of apoptosis and cell survival proteins including PI3K, Akt and GSK3ß and matrix metalloproteinase MMP2 and MMP9 by Western blot method. The antitumor activity of GAE was analyzed in a tumor model of Zebrafish. RESULTS: The outcomes of the in vitro analysis showed an inhibition of cell proliferation, induction of apoptosis, inhibition of cell migration and colonization by the crude extract. The analysis of protein expression showed the activation of caspases 3 and Pro apoptotic protein Bax accompanied by decreased expression of Bcl-2 and Bcl-XL. On the other hand, subsequent activation of GSK3ß and down regulation of PI3K, Akt were observed. The decreased expression of MMP2 correlated with the antimetastatic activity of the extract. The in vivo studies showed an inhibition of tumor growth by GAE in Zebrafish. CONCLUSION: The phytoconstituents of algal extract contributed to the anticancer properties as evidenced by in vitro and in vivo studies. These phytoconstituents can be considered as a natural source of PI3K/Akt inhibitor for treatment of cancers involving the PI3K cascade.

Identification of potential phytochemicals and their inhibitory effect on the PERK receptor mediated UPR pathway for neuronal disease regulation: an in silico insight.

The endoplasmic reticulum (ER) has been considered as the key site of protein biosynthesis and maturation in the eukaryotic cell. In recent years, the sequence at the N-terminal region of translated protein has shown a particular emphasis as a signal responsible for site-specific translocation mediated by post-translational modification. Once the native conformation is not achieved, the degradation pathway is activated, and therefore the restoration of the homeostasis of ER function in UPR pathway is initiated. One of the transmembrane proteins, PKR-like ER kinase (PERK) plays a key role in the activation of UPR through the inhibition of the translation process, thus preventing the cells from apoptosis due to chronic ER stress. Dysregulation of the neuronal proteostasis often results in neuronal dysfunction and its crucially associated neurodegenerative diseases or its manifestation of neuropathic pain. The correlation between ER stress and its associated signaling cascade, namely UPR, is well established in context of neuropathological modifications. This furthermore suggests that the proteins of the signaling cascade such as PERK can serve as a potential target during the onset of neuronal damage. The aim of this study was to identify the potential phytocompounds by evaluating the physicochemical properties, Lipinski screening, ADMET and toxicity properties of the selected phytocompounds by using SwissADME, MolInspiration and pKCSM webservers, which could establish a comparatively better affinity and binding energy than the control drug as GSK2606414 in set up the treatment of the neuronal diseases through molecular docking via PyRx and validating their structural stability through simulation using the Sybyl software for over100ns.Communicated by Ramaswamy H. Sarma.

An idiosyncratic MIMBO-NBRF based automated system for child birth mode prediction.

Predicting the mode of child birth is still remains one of the most complex and challenging tasks in ancient times. Also, there is no such strong methodologies are developed in the conventional works for birth mode prediction. Therefore, the proposed work objects to develop a novel and distinct optimization based machine learning technique for creating the child birth mode prediction system. This framework includes the modules of data imputation, feature selection, classification, and prediction. Initially, the data imputation process is performed to improve the quality of dataset by normalizing the attributes and filling the missed fields. Then, the Multivariate Intensified Mine Blast Optimization (MIMBO) technique is implemented to choose the best set of features by estimating the optimal function. After that, an integrated Naïve Bayes - Random Forest (NBRF) technique is developed by incorporating the functions of conventional NB and RF techniques. The novel contribution of this technique, a Bird Mating (BM) optimization technique is used in NBRF classifier for estimating the likelihood parameter to generate the Bayesian rules. The main idea of this paper is to develop a simple as well as efficient automated system with the use of hybrid machine learning model for predicting the mode of child birth. For this purpose, advanced algorithms such as MIMBO based feature selection, and NBRF based classification are implemented in this work. Due to the inclusion of MIMBO and BM optimization techniques, the performance of classifier is greatly improved with low computational burden and increased prediction accuracy. Moreover, the combination of proposed MIMBO-NBRF technique outperforms the existing child birth prediction methods with superior results in terms of average accuracy up to 99 %. In addition, some other parameters are also estimated and compared with the existing techniques for proving the overall superiority of the proposed framework.

Comparative Study of Effects of Endophytic Fungal Silver Nanoparticles and Nanoemulsion on Escherichia coli.

Green nanotechnology, a branch of nanotechnology, makes use of extract from plants or microorganisms to synthesize nanoparticles. This approach is eco-friendlier and more cost-effective than conventional methods of nanoparticle synthesis. Silver nanoparticles have interested researchers because several studies suggest that they have a wide range of applications in the field of medicine; it is known to serve as a good antimicrobial agent. This study concentrated on the synthesis of silver nanoparticles and nanoemulsion from the extract of an endophytic fungi-Lasiodiplodia theobromae. Nanoemulsion was prepared using an essential oil-tea tree oil from Melaleuca alternifolia (commonly known as tea tree). The nanoparticles were characterized using UV-visible spectra, SEM, FESEM, EDAX, XRD, and FTIR analysis. A comparative antimicrobial study was carried out between endophytic fungal extract-derived nanoparticles (EFNP) and nanoemulsion (EFNE) against two strains of Escherichia coli, through various experimental assays including Agar well diffusion method and assays that determined the minimum inhibitory concentration, minimum bactericidal concentration, and biofilm formation. From the results obtained, it was evident that both EFNP and EFNE had antibacterial activity and that the EFNE worked better than the former. This study suggested that EFNE was a good antibiotic alternative, and further in vivo studies must be done to check the efficacy.

A Study on the Bacteriological Profile of Ascitic Fluids and Their Antibiotic Susceptibility Pattern in a Tertiary Care Hospital.

Background Ascitic fluid culture remains an essential step in the management of all patients with ascites, regardless of their presenting complaints. Diagnostic paracentesis should not be delayed or prevent timely administration of antibiotics, particularly in unstable patients. Hence, it is an essential part of the surveillance system of every hospital to perform ascitic fluid culture and assess the antibiotic susceptibility patterns of bacterial isolates. In view of this perspective, the present study was conducted at Chengalpattu Medical College Hospital, Tamil Nadu, India. Objective The aim of the study is to determine the bacterial isolates of ascitic fluid samples and study their antibiotic susceptibility patterns. Materials and methods Ascitic fluids received in the central laboratory at the Department of Microbiology from various departments were included in this study. Preliminary identification of isolates was performed by direct Gram staining, acid-fast staining, and motility testing by the hanging drop method. Within one hour of receiving the samples, they were plated onto blood agar and MacConkey agar media and incubated for 18-24 hours at 37°C for isolation. Growth was checked, and species identification was done based on conventional methods. Antibiotic susceptibility testing was performed using the Kirby-Bauer disk diffusion method. Results In this study, a total of 100 ascitic fluid samples were collected, of which only eight (8%) showed growth. Among the eight isolates, six (75%) were Gram-negative bacilli (GNB). Four (66.66%) of the six GNB were Klebsiella spp., while the remaining two (33.33%) were Escherichia coli. Both Gram-positive cocci were Staphylococcus aureus. All the GNB isolates were susceptible to meropenem, piperacillin-tazobactam, and ceftriaxone, with varying susceptibilities to other drugs. Both Gram-positive isolates were found to be methicillin-sensitive Staphylococcus aureus. Conclusion GNB were the predominant organisms in cases of ascitic fluid infection, and they showed 100% susceptibility to carbapenem drugs (especially meropenem), piperacillin-tazobactam, and ceftriaxone. All these drugs can be kept in reserve for serious infections. Amikacin and gentamicin showed promising susceptibility. These drugs can be started empirically with patients on admission before performing culture. Drug adjustments may be later made based on culture reports.

Phytocompounds From Edible Oil Seeds Target Hub Genes To Control Breast Cancer.

Breast cancer is one of the most commonly diagnosed cancers in woman which accounts for more than 1 in 10 new cancers in the entire world. The recently found four new potential hub genes that show a strong expression in breast cancer are CCNA2, CCNB1, MAD2L1, and RAD51. Nowadays, food habits and lifestyle of an individual are one of the factors for causing cancers. Consumption of seeds on a regular basis is the key factor for leading a good health. Sesame seeds and Sunflower seeds are few examples of cancer fighting seeds. Sesame (Sesamum indicum) is one of the earliest oil seed plant with various phytocompounds present which include lignans, tocopherols, phenolics, polyunsaturated fatty acids, and phytosterols. Sunflower (Helianthus annuus L.) is primarily harvested as an oil seed plant with various phytocompounds present which include flavonoids, phenolic acids, tocopherols, and vitamin B3. These are the few seeds that help women to prevent and also to fight against Breast cancer with its potential anti-cancer activity. The main objective of the current study is to identify the potential phytocompounds present in the cancer fighting seeds using molecular docking and dynamic simulation approach which can further help pharmaceuticals industries in producing targeted drugs against breast cancer hub genes as well as food industries in producing products combining the potential phytocompounds present in the seeds.

Mimusops elengi Flower-Mediated Green Silver Nanoparticles Control Staphylococcus aureus and Acinetobacter baumannii.

The use of antibiotics against infection-causing bacteria is inactivated, due to the presence of antibiotic-degrading enzymes. These enzymes resist the action of antibiotics and make difficult for the already existing antibiotics to break the drug resistance. Hence, there is a need to formulate alternate therapies against the enzymes providing multidrug resistance to bacteria including Staphylococcus aureus and Acinetobacter baumannii. A silver nanoparticle coated with the natural compounds is a way of finding an alternative to the traditional antibiotics. Objective of the study was to identify and assess Mimusops elengi's floral silver nanoparticles (MENP) for its effective antibacterial activity. The methods involved were in silico analysis involving screening by ADME; drug likeness and docking of ligand to the protein (CrtM and CTX-M-15); in vitro analysis which included silver nanoparticle preparation; characterization by UV-Vis spectrum; SEM, FT-IR, DLS, and antimicrobial assays which include agar well diffusion, minimum inhibitory concentration, minimum bactericidal concentration, and anti-biofilm assays. The compounds present in the flower extract were identified and their usability against the enzymes under study was assured by silico screening. The in vitro analysis furthermore supports through showing potent antibacterial activity of MENP against selected organisms. Hence both in silico and in vitro studies reveal that MENP can be used as an alternative to break multidrug resistance.

Artificial Intelligence-Based Smart Comrade Robot for Elders Healthcare with Strait Rescue System.

A rising proportion of older people has more demand on services including hospitals, retirement homes, and assisted living facilities. Regaining control of this population's expectations will pose new difficulties for lawmakers, medical professionals, and the society at large. Smart technology can help older people to have independent and fulfilling lives while still living safely and securely in the community. In the last several decades, the number of sectors using robots has risen. Comrade robots have made their appearance in old human life, with the most recent notable appearance being in their care. The number of elderly individuals is increasing dramatically throughout the globe. The source of the story is the use of robots to help elderly people with day-to-day activities. Speech data and facial recognition model are done with AI model. Here, with the Comrade robotic model, elder people's healthcare system is designed with better analysis state. The aim is to put in place a simple robotic buddy to determine the health of the old person via a headband that has been given to them. Comrade robot may do things like senior citizens home automation, home equipment control, safety, and wellbeing sensing, and, in emergency situation, routine duties like navigating in the outside world. The fear that robotics and artificial intelligence would eventually eliminate most of the jobs is increasing. It is anticipated that, in order to survive and stay relevant in the constantly shifting environment of work, workers of the future will need to be creative and versatile and prepared to identify new business possibilities and change industry to meet challenges of the world. According to the research, reflective practice, time management, communicating, and collaboration are important in fostering creativity.

Emergence of novel Porcine circovirus 2 genotypes in Southern India.

A total of 200 samples from Porcine circovirus 2 suspected (n = 112) and healthy (n = 88) swine populations collected from different districts of Tamil Nadu, south India were used in this study. The samples comprising of serum (n = 124), swabs from natural orifices (n = 52), and postmortem tissues (n = 24). All the samples were processed and subjected to the screening and detection of the PCV2 genome by a specific PCR assay. PCV2 genomes from positive samples were further subjected to genotyping with specifically designed primers for the full-length amplification of the ORF2 gene which codes for capsid protein (Cp) and serves as an epidemiological marker. Randomly, 13 amplified ORF2 genes were sequenced and the aligned sequences were subjected to signature motif analysis and phylogeny in MEGA X. The molecular prevalence of PCV2 infection in Tamil Nadu is 10.5% (n = 21). Signature motif and phylogenetic studies of 13 samples revealed 38.5% (n = 5) presence of each PCV2b intermediate 1(IM1) and PCV2b genotypes, followed by 15.4% (n = 2) PCV2d-2 and 7.7% (n = 1) PCV2d genotypes. The PCV2b-IM1 genotype has a 99.43% sequence homology with Vietnam isolate (JX506730). PCV2b genotypes showed 99.72% sequence identity with Chinese isolate (KX068219). PCV2d-2 genotypes reported in this study have 100% sequence identity with Taiwan isolate (MF169721). PCV2d genotype showed 97.87% sequence identity with Thailand isolate (MF314293). Amino acid analysis of all the 13 full-length ORF2 gene sequences revealed specific mutations in the immune reactive domains of A, B, C, and D. Capsid protein of three PCV2b and five PCV2b IM1 isolates had extra amino acid residue lysine (K) at 234 position of ORF2 similar to PCV2d. For the first time in South India, PCV2b IM1 and PCV2d-2 genotypes are reported. This study evidences the genetic shifts of PCV2 isolates in India and it is analogous to that of global genotypic shift.