Evaluation of the inhibitory potential of bioactive compounds against SARS-CoV-2 by in silico approach.

CONTEXT: The COVID-19 (coronavirus disease 19) pandemic brought on by the SARS-CoV-2 outbreak (severe acute respiratory syndrome coronavirus 2) has stimulated the exploration of various available chemical compounds that could be used to treat the infection. This has driven numerous researchers to investigate the antiviral potential of several bioactive compounds from medicinal plants due to their reduced adverse effects compared to chemicals. Some of the bioactive compounds used in folklore treatment strategies are reported as effective inhibitors against the proliferative and infective cycles of SARS-CoV-2. The secondary metabolites from plants are generally used to treat various diseases due to their intact medicinal properties. The present study analyzes the inhibitory potential of phytochemicals from medicinal plants like Sphaeranthus indicus, Lantana camara, and Nelumbo nucifera against SARS-CoV-2 by molecular docking. METHODS: Ten druggable protein targets from SARS-CoV-2 are docked against the phytochemicals from the selected medicinal plants. The phytocompounds astragalin, isoquercetin, and 5-hydroxy-7-methoxy-6-c-glycosy flavone were found to have lower binding energy depicting their inhibitive potential compared with the reported inhibitors that are used in the treatment of SARS-CoV-2 infection. The phytocompounds found to have the least binding energy were selected for further analyses. To assess the compounds' potential as drugs, their ADMET characteristics were also examined. Sphaeranthus indicus, Lantana camara, and Nelumbo nucifera six possible compounds were separately screened for ADME and toxicity characteristics; then, the results were analyzed. To assess the impact of the phytocompound binding on the dynamics of SARS-CoV-2 ribonuclease protein NSP15, microsecond-level all atomistic molecular dynamics simulations were performed, and their dynamics were analyzed. Microsecond-level molecular dynamics simulations of both the ligands complexed with NSP15 revealed that the ligand induces allosteric effects on NSP15, which could lead to destabilization of NSP15 hexameric interface and loss of RNA binding. The low binding energy exhibited by the phytochemicals from Lantana camera, Sphaeranthus indicus, and Nelumbo nucifera against the protein targets of SARS-CoV-2 showed inhibitory potential by the selected molecules. Their predicted interference of the enzymes involved in the molecular mechanisms aiding the proliferation of SARS-CoV-2 indicated the inhibitive ability of the phytochemicals.

Outcomes of ab-interno irrigating goniectomy with trabectome in primary and secondary glaucoma from a single center in India.

Purpose: This study was done to report intermediate-term outcomes of irrigating goniectomy with trabectome (trabectome) surgery among different types of glaucoma eyes from a single center in India using a cross-sectional, longitudinal, observational study design. Methods: Fifty-three patients (58 eyes) with glaucoma who underwent irrigating goniectomy with trabectome between January 2019 and February 2020 were included. Pre-operative data included age, gender, eye laterality, specific diagnosis, number of anti-glaucoma medications (AGMs), prior glaucoma surgeries, visual acuity, and intraocular pressure (IOP) on medical treatment. Post-operative data included IOP changes during the follow-up till 1-year, number of AGMs, any complications, or additional surgical intervention required. Success was defined as IOP ≤ 21 mmHg and ≥ 20% reduction of IOP from pre-operative IOP with no additional glaucoma surgery. Results: The cohort included 58 eyes (male 53.4% and female 46.6%) ranging from 0.6 to 81 years of age. The average baseline IOP was 23.4 ± 10.2 mmHg and reduced significantly with surgery to 14.1 ± 5.3 mmHg at 1-year follow-up. The AGMs reduced from 2.4 ± 1.4 pre-surgery to 1.6 ± 1.4 at 1-year follow-up. Four eyes required additional glaucoma surgeries for IOP control. The success rate of trabectome with phacoemulsification (88%) was discernibly higher than with trabectome alone (67%). Intra-operatively, significant blood reflux was noticed in 27 eyes, of which only one required tamponading with a viscoelastic agent. Conclusion: This study concludes that irrigating goniectomy with trabectome has good efficacy and safety in both pediatric and adult cases of glaucoma in terms of IOP control, reduction in AGMs, and low incidence of complications in the Indian population.

Isoeugenol suppresses multiple quorum sensing regulated phenotypes and biofilm formation of Pseudomonas aeruginosa PAO1.

The potential strategy to prevent bacterial pathogenicity is disabling quorum sensing circuits with structural mimicking molecules. Here, we analyzed a synthetic molecule isoeugenol, for inhibition of quorum sensing regulated phenotype and biofilm formation. Isoeugenol was an effective inhibitor, i.e., more than 70% of virulence factors were inhibited including pyocyanin, rhamnolipid, exopolysaccharide, swarming motility and biofilm formation. Interestingly, these quorum sensing regulated phenotypes in Pseudomonas aeruginosa PAO1 were inhibited without affecting the planktonic cells. Moreover, the presence of isoeugenol exhibited more than 70% inhibition of biofilm formation through inhibition of the quorum sensing systems. Furthermore, docking studies suggest that isoeugenol bound to the quorum sensor regulators such as LasI, LasR PqsE and SidA with considerable binding interactions. Our results demonstrate the utility of isoeugenol as a blocker of quorum sensing, which will be functioning as an antivirulence compound.

The diversity of unique 1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid coding common genes and Universal stress protein in Ectoine TRAP cluster (UspA) in 32 Halomonas species.

OBJECTIVES: To decipher the diversity of unique ectoine-coding housekeeping genes in the genus Halomonas. RESULTS: In Halomonas, 1,4,5,6-Tetrahydro-2-methyl-4-pyrimidinecarboxylic acid has a crucial role as a stress-tolerant chaperone, a compatible solute, a cell membrane stabilizer, and a reduction in cell damage under stressful conditions. Apart from the current 16S rRNA biomarker, it serves as a blueprint for identifying Halomonas species. Halomonas elongata 1H9 was found to have 11 ectoine-coding genes. The presence of a superfamily of conserved ectoine-coding among members of the genus Halomonas was discovered after genome annotations of 93 Halomonas spp. As a result of the inclusion of 11 single copy ectoine coding genes in 32 Halomonas spp., genome-wide evaluations of ectoine coding genes indicate that 32 Halomonas spp. have a very strong association with H. elongata 1H9, which has been proven evidence-based approach to elucidate phylogenetic relatedness of ectoine-coding child taxa in the genus Halomonas. Total 32 Halomonas species have a single copy number of 11 distinct ectoine-coding genes that help Halomonas spp., produce ectoine under stressful conditions. Furthermore, the existence of the Universal stress protein (UspA) gene suggests that Halomonas species developed directly from primitive bacteria, highlighting its role during the progression of microbial evolution.

Bio-corrosion impacts on mechanical integrity of ZM21 Mg for orthopaedic implant application processed by equal channel angular pressing.

The mechanical integrity of rolled ZM21 Mg was improved by equal channel angular pressing (ECAP) to function as a potential biodegradable bone screw implant. Electron backscattered diffraction (EBSD) revealed deformed grains of 45 µm observed in rolled ZM21 Mg. They were transformed to equiaxed fine grains of 5.4 µm after 4th pass ECAP. The yield strength of rolled and ECAPed ZM21 Mg alloys were comparable. In contrast, 4th pass ZM21 Mg exhibited relatively higher elongation when compared to rolled sample. The mechanical properties of rolled and ECAPed ZM21 Mg were dependant on both grain refinement and crystallographic texture. The rolled and 4th pass ECAPed tensile samples exhibited nonlinear deterioration of mechanical properties when tested after 7, 14, 21 and 28 days immersion in Hank's solution. The evaluation signifies that regardless their processing condition, ZM21 Mg alloys are suitable for surgical areas that requires high mechanical strength. In addition, the 4th pass ECAP samples were viable to MG-63 cells proving themselves to be promising candidates for future in vivo studies.

Pregnancy Outcomes Post-bariatric Surgery-a Single-Centre Retrospective Study from India.

BACKGROUND: Bariatric surgery presently is the best possible intervention for treatment of severe obesity and its related conditions. This study presents retrospective data on the pregnancy outcomes of Indian patients who underwent bariatric surgery before conception. METHODOLOGY: This is a single-centre retrospective, observational study. Data on demographics, pre-surgery weight, body mass index (BMI), types of bariatric surgery, weight at conception, weight gain during pregnancy, type of delivery and the health of the baby were collected and analysed to study the weight loss pattern and pregnancy outcomes in female patients of childbearing potential. RESULTS: The study included 34 women of childbearing potential (BMI>30 kg/m2) who underwent bariatric surgery. The study population was followed up from the time of surgery until 1-year post-delivery of the baby. The mean weight gain during the pregnancy was 14.9±5.4 kg. Twenty-three underwent LSCS, and the rest had normal delivery with mean baby weight of 2.5±0.4 kg. Six babies required neonatal intensive care. In our series, only 4 of 35 cohorts that are only 11% had substantial weight retention (range 5-13 kg) at the end of 12 months which is significantly lower than the normal cohorts who did not undergo bariatric surgery. CONCLUSION: Bariatric surgery improves fertility with safe pregnancy and its outcomes in terms of preeclampsia, eclampsia, gestational diabetes, premature rupture of the membranes (PROM), postpartum haemorrhage (PPH) and puerperal sepsis in women with childbearing potential and safe for offspring in terms of shoulder dystocia, macrosomia, birth asphyxia and perinatal mortality. However, they should be well aware of the risks associated with bariatric surgery especially the mal-absorptive procedures.

Agricultural management practices influence the soil enzyme activity and bacterial community structure in tea plantations.

BACKGROUND: The soil quality and health of the tea plantations are dependent on agriculture management practices, and long-term chemical fertilizer use is implicated in soil decline. Hence, several sustainable practices are used to improve and maintain the soil quality. Here, in this study, changes in soil properties, enzymatic activity, and dysbiosis in bacterial community composition were compared using three agricultural management practices, namely conventional (CA), sustainable (SA), and transformational agriculture (TA) in the tea plantation during 2016 and 2017 period. Soil samples at two-months intervals were collected and analyzed. RESULTS: The results of the enzyme activities revealed that acid phosphatase, arylsulfatase, ß-glucosidase, and urease activities differed considerably among the soils representing the three management practices. Combining the redundancy and multiple regression analysis, the change in the arylsulfatase activity was explained by soil pH as a significant predictor in the SA soils. The soil bacterial community was predominated by the phyla Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, and Bacteroidetes in the soil throughout the sampling period. Higher Alpha diversity scores indicated increased bacterial abundance and diversity in the SA soils. A significant relationship between bacterial richness indices (SOBS, Chao and ACE) and soil pH, K and, P was observed in the SA soils. The diversity indices namely Shannon and Simpson also showed variations, suggesting the shift in the diversity of less abundant and more common species. Furthermore, the agricultural management practices, soil pH fluctuation, and the extractable elements had a greater influence on bacterial structure than that of temporal change. CONCLUSIONS: Based on the cross-over analysis of the bacterial composition, enzymatic activity, and soil properties, the relationship between bacterial composition and biologically-driven ecological processes can be identified as indicators of sustainability for the tea plantation.

A descriptive analysis of antimicrobial resistance patterns of WHO priority pathogens isolated in children from a tertiary care hospital in India.

The World Health Organization (WHO) has articulated a priority pathogens list (PPL) to provide strategic direction to research and develop new antimicrobials. Antimicrobial resistance (AMR) patterns of WHO PPL in a tertiary health care facility in Southern India were explored to understand the local priority pathogens. Culture reports of laboratory specimens collected between 1st January 2014 and 31st October 2019 from paediatric patients were extracted. The antimicrobial susceptibility patterns for selected antimicrobials on the WHO PPL were analysed and reported. Of 12,256 culture specimens screened, 2335 (19%) showed culture positivity, of which 1556 (66.6%) were organisms from the WHO-PPL. E. coli was the most common organism isolated (37%), followed by Staphylococcus aureus (16%). Total of 72% of E. coli were extended-spectrum beta-lactamases (ESBL) producers, 55% of Enterobacteriaceae were resistant to 3rd generation cephalosporins due to ESBL, and 53% of Staph. aureus were Methicillin-resistant. The analysis showed AMR trends and prevalence patterns in the study setting and the WHO-PPL document are not fully comparable. This kind of local priority difference needs to be recognised in local policies and practices.

Is weight regaining significant post laparoscopic Roux-en-Y gastric bypass surgery? - A 5-year follow-up study on Indian patients.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (RYGB) has been proven to induce significant weight loss and remission of related co-morbidities in patients with morbid obesity. The long-term follow-up data show weight regain or failure to achieve complete remission of type 2 diabetes mellitus (T2DM) in some patients. In this study, we report weight loss patterns and remission of T2DM in patients with morbid obesity during a 5-year follow-up after RYGB. OBJECTIVE: The objective was to evaluate outcomes during the follow-up on excess weight loss (EWL) and remission of T2DM after laparoscopic RYGB among Indian patients. SETTING: The study was conducted in a tertiary care hospital, Kerala, India. MATERIALS AND METHODS: This is a retrospective study in patients who underwent surgery between 2007 and 2010. The patient demographics, pre- and post-operative body mass index (BMI), co-morbidities and EWL were recorded from the medical records. These data were compared between pre-operative and follow-up intervals till 5 years using statistical approaches. RESULTS: The study included 157 patients (91 males and 66 females) having a mean pre-operative BMI of 47.91 ± 7.01 kg/m2. A significant reduction in the BMI was observed at each follow-up point (P < 0.01) till 5 years after the surgery. The mean percentage of EWL increased from 34.57% ± 12.62% to 71.50% ± 15.41% from 3 months to 5 years after the surgery. Twelve per cent (n = 19) of patients achieved normal BMI (<25 mg/kg2) by 3rd year after the surgery. However, the remission of T2DM was achieved in >50% of patients within a year of surgery. During the 5th year, weight regain (1-22 kg) was observed in 36.70% (n = 58) patients, and recurrence of T2DM was observed in two patients. CONCLUSIONS: The long-term durability of RYGB in the study population was satisfactory with significant weight loss and remission of T2DM.

Genome analysis of a halophilic bacterium Halomonas malpeensis YU-PRIM-29T reveals its exopolysaccharide and pigment producing capabilities.

Halomonas malpeensis strain YU-PRIM-29T is a yellow pigmented, exopolysaccharide (EPS) producing halophilic bacterium isolated from the coastal region. To understand the biosynthesis pathways involved in the EPS and pigment production, whole genome analysis was performed. The complete genome sequencing and the de novo assembly were carried out using Illumina sequencing and SPAdes genome assembler (ver 3.11.1) respectively followed by detailed genome annotation. The genome consists of 3,607,821 bp distributed in 18 contigs with 3337 protein coding genes and 53% of the annotated CDS are having putative functions. Gene annotation disclosed the presence of genes involved in ABC transporter-dependent pathway of EPS biosynthesis. As the ABC transporter-dependent pathway is also implicated in the capsular polysaccharide (CPS) biosynthesis, we employed extraction protocols for both EPS (from the culture supernatants) and CPS (from the cells) and found that the secreted polysaccharide i.e., EPS was predominant. The EPS showed good emulsifying activities against the petroleum hydrocarbons and its production was dependent on the carbon source supplied. The genome analysis also revealed genes involved in industrially important metabolites such as zeaxanthin pigment, ectoine and polyhydroxyalkanoate (PHA) biosynthesis. To confirm the genome data, we extracted these metabolites from the cultures and successfully identified them. The pigment extracted from the cells showed the distinct UV-Vis spectra having characteristic absorption peak of zeaxanthin (λmax 448 nm) with potent antioxidant activities. The ability of H. malpeensis strain YU-PRIM-29T to produce important biomolecules makes it an industrially important bacterium.

Bacterial cross talk with gut microbiome and its implications: a short review.

Human gut microbiota exists in a complicated symbiotic relationship which postulates to impact health and disease conditions on the host. Interestingly, the gut microbiome shows different mechanisms to regulate host physiology and metabolism including cell-to-cell communications. But microbiota imbalance is characterized to change in the host normal functioning and lead to the development and progression of major human diseases. Therefore, the direct cross talk through the microbial metabolites or peptides suggests the evidence of host health and disease. Recent reports highlight the adaptation signals/small molecules promoting microbial colonization which allows modulating immunity of host and leads to pathogen colonization. Moreover, quorum sensing peptides are also evident in the involvement of host disease conditions. Here, we review the current understanding of the gut microbiota cross talk with mammalian cells through metabolites and peptides. These studies are providing insight into the prediction of signature molecules which significantly provide information for the understanding of the interaction for precision medicine applications.

Bioresponsive supramolecular hydrogels for hemostasis, infection control and accelerated dermal wound healing.

Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Demineralization of tooth enamel following radiation therapy; An in vitro microstructure and microhardness analysis.

OBJECTIVE: The objective of this study is to evaluate the effects of radiotherapy doses on mineral density and percentage mineral volume of human permanent tooth enamel. MATERIALS AND METHODS: Synchrotron radiation Xray microcomputed tomography (SRµCT) and microhardness testing were carried out on 8 and 20 tooth samples, respectively. Enamel mineral density was derived from SRµCT technique using ImageJ software. Microhardness samples were subjected to Vickers indentations followed by calculation of microhardness and percentage mineral volume values using respective mathematical measures. Data were analyzed using paired t-test at a significance level of 5%. Qualitative analysis of the enamel microstructure was done with two-dimensional projection images and scanned electron micrographs using µCT and field emission scanning electron microscopy, respectively. RESULTS: Vickers microhardness and SRµCT techniques showed a decrease in microhardness and an increase in mineral density, respectively, in postirradiated samples. These changes were related to mineral density variation and alteration of hydroxyapatite crystal lattice in enamel surface. Enamel microstructure showed key features such as microporosities and loss of smooth homogeneous surface. These indicate tribological loss and delamination of enamel which might lead to radiation caries. CONCLUSIONS: Tooth surface loss might be a major contributing factor for radiation caries in head-and-neck cancer patients prescribed to radiotherapy. Such direct effects of radiotherapy cause enamel abrasion, delamination, and damage to the dentinoenamel junction. Suitable measures should, therefore, be worked out to protect nontarget oral tissues such as teeth while delivering effective dosages to target regions.

Microwave-assisted rapid synthesis of silver nanoparticles using fucoidan: Characterization with assessment of biocompatibility and antimicrobial activity.

Silver nanoparticles (AgNPs) have gained attention due to their exceptional physicochemical properties and biological activities, owing to which they are extensively used in biomedical field. We synthesized AgNPs by rapid microwave-assisted method using fucoidan as a reducing agent. The synthesized fucoidan-AgNPs (F-AgNPs) were characterized for the structural and functional properties. The bactericidal effect and mode of action of F-AgNPs on the pathogenic bacteria and biofilm formation were investigated along with the cytotoxicity studies. The UV-Visible spectra of the F-AgNPs showed the surface resonance peak at 419 nm. The nanoparticles were spherical in shape with particle size of 59.5 ± 1.46 nm and polydispersity index (PDI) of 0.3 ± 0.01. Capping of fucoidan on AgNPs was confirmed by FTIR with characteristic peaks of sulfate group. Silver content of F-AgNPs was 87% with 13% contribution from the fucoidan moieties. The F-AgNPs showed antimicrobial activity against common pathogenic bacteria and was able to inhibit biofilm formation in Pseudomonas aeruginosa at 20 µg/mL concentration. The oxidative stress and intracellular protein leakage were observed due to the F-AgNP interaction with the cell bringing about bactericidal effect. The results highlight the synthesis and bioactivity of AgNPs doped with organic moieties for applications as antimicrobials.

A novel exopolysaccharide from marine bacterium Pantoea sp. YU16-S3 accelerates cutaneous wound healing through Wnt/ß-catenin pathway.

Natural polysaccharides with versatile properties are the potential candidates for wound healing applications. In this study, an exopolysaccharide, EPS-S3, isolated from a marine bacteria Pantoea sp. YU16-S3 was evaluated for its wound-healing abilities by studying the key molecular mechanisms in vitro and in vivo. Basic characterisation showed EPS-S3 as a heteropolysaccharide with glucose, galactose, N-acetyl galactosamine and glucosamine. The molecular weight of EPS-S3 was estimated to be 1.75 × 105 Da. It showed thermal stability up to 200 °C and shear-thickening non-Newtonian behaviour. It was biocompatible with dermal fibroblasts and keratinocytes and showed cell adhesion and cell proliferation properties. EPS-S3 facilitated cell migration in fibroblasts, induced rapid transition of cell cycle phases and also activated macrophages. In vivo experiments in rats showed the re-epithelialization of injured tissue with increased expression of HB-EGF, FGF, E-cadherin and ß-catenin in EPS-S3 treatment. The results indicate that EPS-S3 modulates healing process through Wnt/ß-catenin pathway due to its unique characteristics. In conclusion, EPS-S3 biosynthesized by the marine bacterium is a potential biomolecule for cutaneous wound healing applications.

The whole-genome sequence analysis of Enterobacter cloacae strain Ghats1: insights into endophytic lifestyle-associated genomic adaptations.

Enterobacter cloacae is normally considered to be an opportunistic human pathogen. Here, we report on the whole-genome sequence of an endophytic E. cloacae, strain "Ghats1", isolated from leaves of the medicinal plant Coscinium fenestratum Gaertn. Functional analysis of the Ghats1 genome revealed an enrichment for genes involved in the uptake and exchange of nutrients, for chemotaxis and for plant colonization. Unexpectedly though, there were no ORFs belonging to the "virulence factors and antibiotic resistance". Moreover, the presence of hydrolytic enzymes and motility functions reveals the characteristics of an endophyte lifestyle of a bacterium that can colonize and adapt to plant environment. These results provide a better understanding of an endophytic lifestyle through plant-microbe interaction, which can be further exploited as a biocontrol agent.

Spectroscopic analyses reveal radiotherapy-induced variations in elemental composition and crystallite properties of human permanent teeth enamel.

OBJECTIVE: To study the effect of radiation therapy on the structural and elemental composition of permanent teeth enamel in vitro. METHODS: Sections from 21 noncarious healthy human teeth were exposed to a cumulative radiation dose of 20-80 Gy. The sections were subjected to electron dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis to study the elemental composition, the ratio of inorganic and organic content, and the mineralization and crystalline properties of the hydroxyapatite crystal structure respectively. All measures were taken on specified areas of enamel surface before and after radiation exposure and compared. RESULTS: In FTIR and EDS studies, the calcium to phosphorus (Ca/P) and carbonate to phosphate (CO32-/PO3-4) ratios were significantly different (P < 0.05) in teeth sections exposed to 80 Gy, indicating the deterioration of inorganic calcium and phosphorous content. The XRD spectrum data showed loss of peaks at seven specific 2θ coordinate areas, flattened peaks and an increase in the crystallite size in the radiation-exposed groups due to mineralization loss and alteration of the hydroxyapatite crystal matrix in the tooth enamel. CONCLUSIONS: Radiotherapy can induce significant variations in the inorganic and organic functional groups constituting the tooth enamel surface; and these variations are dose dependent. The mechanism responsible for delamination and radiation caries needs to be explored by studying the protein lysis pattern, which might be a leading factor causing the enamel degradation and radiation caries.

Tetrandrine isolated from Cyclea peltata induces cytotoxicity and apoptosis through ROS and caspase pathways in breast and pancreatic cancer cells.

Tetrandrine is a bisbenzylisoquinoline alkaloid known to exhibit anticancer activity against different cancers. In the present study, the cytotoxic effect of tetrandrine isolated from Cyclea peltata on pancreatic (PANC-1) and breast (MDA-MB-231) cancer cells was evaluated in vitro with an attempt to understand the role of tetrandrine on the generation of reactive oxygen species (ROS) and caspase activation. Results demonstrate the dose- and time-dependant cytotoxic effect of tetradrine on both MDA-MB-231 and PANC-1 cells with IC50 values ranging between 51 and 54 µM and 22 and 27 µM for 24 h and 48 h of incubation respectively. In addition, treatment of MDA-MB-231 and PANC-1 cells with tetrandrine showed the shrunken cytoplasm and damaged cell membrane in a dose- and time-dependant manner under the microscope. Also, tetrandrine treatment revealed an elevated levels of reactive oxygen species and increased activities of caspase-8, -9 and -3 confirming the apoptosis of cells through both extrinsic death receptor and intrinsic caspase activation. Therefore, the present study suggests the apoptosis of cells with the activation of caspase pathways mainly intrinsic pathway as a downstream event of tetrandrine-induced ROS generation. Hence, reactive oxygen species-mediated caspase activation pathway may be potentially targeted with the use of tetrandrine to treat breast and pancreatic cancers.

A bioactive exopolysaccharide from marine bacteria Alteromonas sp. PRIM-28 and its role in cell proliferation and wound healing in vitro.

Marine bacteria secrete exopolysaccharides (EPS) with unique structural and functional properties and serve as a source of newer bioactive biopolymers. This study reports an EPS produced by a marine bacterium identified as Alteromonas sp. PRIM-28 for its bioactivities. The EPS was characterised using standard methods and tested for its bioactivities using in vitro models. EPS-A28 is an anionic heteropolysaccharide with a molecular weight of 780 kDa and exists as triple helical structure in aqueous solution. Monosaccharide composition is mannuronic acid, glucose and N-acetyl glucosamine repeating units in the ratio 1:3.67:0.93. The FT-IR spectra showed the presence of sulphate, phosphate and uronic acid residues. The thermal analysis showed partial degradation of the EPS-A28 at 190 °C and 40% of residues were stable up to 800 °C. It showed biocompatibility and induced proliferation and migration of dermal fibroblasts (HDF) and keratinocytes. EPS-A28 could increase the S-phase of cell cycle. The proliferative property of the EPS-A28 was established by the increased expression of fibroblast proliferation marker (Ki-67) also its capability of binding to cell surface. It also induced nitric oxide and arginase synthesis in macrophages. These findings suggest that EPS-A28 can be potentially used as a multifunctional bioactive polymer in wound care.

Anti-biofilm and cytoprotective activities of quercetin against Pseudomonas aeruginosa isolates.

Increase in infection with multidrug resistant Pseudomonas aeruginosa is a serious global challenge in healthcare. Pseudomonas aeruginosa is capable of causing human infection in various sites and complicates the infection due to its virulence factors. This study was aimed to investigate the effect of quercetin, a dietary flavonoid against the virulence factors of P. aeruginosa and its cell protective effects on epithelial cells. Bactericidal activity, anti-biofilm activity and effect on different virulence factors were carried out using standard methods by using five P. aeruginosa isolates. Cytotoxicity and cell protective effect of quercetin was evaluated by trypan blue dye exclusion assay. All the tested isolates were completely inhibited (100%) by quercetin at a concentration of 500 µg ml-1 . It showed significant (P < 0·05) inhibitory effect on virulence factors including biofilm formation and showed significant protective effect on HEK 293T cells infected with P. aeruginosa strains. This study supports the role of quercetin against P. aeruginosa, by inhibiting virulence factors as well as its cytoprotective activity during bacterial infection either by attenuating the virulence or providing direct protective effect to the host cells. SIGNIFICANCE AND IMPACT OF THE STUDY: The increase in infections caused by opportunistic pathogen Pseudomonas aeruginosa is a serious concern in the health care system. This study describes the beneficial effects of a dietary flavonoid, quercetin against pathogenic P. aeruginosa strains and its protective effect against the P. aeruginosa infection in HEK 293T cells in vitro.