Data-Driven Approaches to Predict Dendrimer Cytotoxicity.

Dendrimers are employed as functional elements in contrast agents and are proposed as nontoxic vehicles for drug delivery. Toxicity is a property that is to be evaluated for this novel class of bionanomaterials for in vivo applications. The current research is hampered due to the lack of structured data sets for toxicity studies for dendrimers. In this work, we have built a data set by curating literature for toxicity data and augmented it with structural and physicochemical features. We present a comprehensive, feature-rich database of dendrimer toxicity measured across various cell lines for prediction, design, and optimization studies. We have also explored novel computational approaches for predicting dendrimer cytotoxicity. We demonstrate superior outcomes for toxicity prediction using essential regression in the space of small data sets.

Imperatorin from the aerial parts of Cleome viscosa L.: a characterization study and evaluation of the antibacterial activity.

Cleome viscosa L., a member of the family Cleomaceae, is a potential medicinal plant, known for several bioactive properties such as: anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, wound healing, etc. Our study aimed to isolate a bioactive compound and assess its antibacterial activity. The crystal compound imperatorin was isolated and reported for the first time from the aerial parts of C. viscosa. The isolation was made using silica gel (100-200 mesh) column chromatography. The structure of imperatorin was investigated through single-crystal XRD, unit cell molecules, FTIR, and ESI-MS spectral analysis. The results validated imperatorin's triclinic crystal structure and P2i/c distance group. The electronic structure was also calculated (4.28/6.21 D) along with the frontier molecular orbital, dipole moment, atomic charges, and electrostatic map of particles in gaseous stage and active site. Imperatorin showed highest activity at 40 µg/mL concentration against Gram + ve bacteria: Staphylococcus aureus (3 ± 0.2 mm), Bacillus subtilis (3 ± 0.6 mm), and Gram -ve bacteria: Klebsiella pneumoniae (3 ± 0.2 mm), Escherichia coli (5 ± 0.2 mm). The study highlights that the compound can be isolated in larger quantities as the plant is easily available across the tropics.

Phages for treatment of Salmonella spp infection.

Salmonella, is one of the bacterial genera having more than 2500 serogroups is one of the most prominent food borne pathogen that is capable of causing disease out breaks among humans and animals. Recent reports clearly shows that this pathogen is evolved and it developed drug resistant towards most of the commercially available antibiotics. In order to overcome this emerging resistance, Bacteriophage therapy is one of the alternative solutions. It is more pathogen specific, high potency, and thereby highly safe for consumption. This chapter discuss about Rapid screening and Detection Methods Associated with Bacteriophage for Salmonella, commercially available phage products and regulatory status, Salmonella endolysins and future prospects of phage therapy.

Phytochemical screening of ethanolic extracts of Cuminum cyminum L. seeds along with the evaluation of antidiabetic properties by molecular docking approach.

In this contribution, ethanolic extracts of Cuminum cyminum (C. cyminum) seeds were evaluated in terms of phytochemical content, total phenol and flavonoid contents. As far as the analytical techniques are concerned, UV-Vis, FTIR, HPLC, NMR (1H and 13C) and ESI-MS were performed. The binding capacity of five different antidiabetic enzymes was tested by in silico molecular docking studies. The HPLC, UV-Vis, FTIR, NMR and ESI-MS data highlighted the presence of seven biologically active molecules e.g. α-pinene, ß-pinene, Δ3-carene, ρ-cymene, α-terpineol, cuminaldehyde and linalool. The results coming from the in silico molecular docking studies showed that such phytochemicals present in the cumin seed extracts play an important role in the activity of key enzymes involved in carbohydrate metabolism. Therefore, C. cyminum is proven to be useful for the treatment of diabetes mellitus and its major secondary complications.

In Silico computational screening of Kabasura Kudineer - Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein.

BACKGROUND: Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds. OBJECTIVE: The study is aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2. METHOD: Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers. RESULTS: Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as "SNACK-V" CONCLUSION: Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.

Investigation of Candidal Species among People Who Suffer from Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma.

AIM AND OBJECTIVE: The aim of the present study was to evaluate the candidal species among masses with oral potentially malignant disorders and oral squamous cell carcinoma. MATERIALS AND METHODS: This prospective and observational study was conducted by the Department of Oral Pathology and Microbiology, S. B. Patil Dental College, Bidar, Karnataka, India, from February 2018 to January 2019. The study composed of total of 150 individuals, of which 50 individuals did not had any visible manifestations, 50 were analyzed with potentially malignant disorders (PMDs) in particular oral leukoplakia, oral lichen planus, and oral submucous fibrosis and last group of 50 individuals were suffering from oral squamous cell carcinoma (OSCC). First, the swab samples were elicited from culture technique after that incisional biopsy of the discernible investigated lesion was done for the purpose of justopathological verification. The swab samples were streak on Sabouraud dextrose agar (SDA) and HiCrome Candida Differential HiVeg agar/CHROMagar medium and incubation at 37°C for 24-48 h. Biopsy was done for all the samples. RESULTS: The proportion of candidates as men and women in control was 45 (90%) and 5 (10%), in PMD was 30 (60%) and 20 (40%), and in OSCC was 45 (90%) and 5 (10%), correspondingly. On evaluation on SDA medium in controls, PMD and OSCC groups, Candida was founded in 14 (28%), 20 (40%), and 42 (84%) and not founded in 36 (72%), 30 (60%), and 8 (16%) folks, subsequently. Intragroup contrast illustrated exceedingly necessary distinction with P = 0.000 between both controls versus OSCC and PMD in comparison to OSCC. Nevertheless, controls versus PMD manifested insignificant, P = 0.119. Investigation on CHROM AGAR media among controls, PMD and OSCC groups, Candida species was seen in 11 (22%), 19 (38%), and 40 (80%) and absent in 39 (78%), 31 (62%), and 10 (20%) individuals, respectively. On statistical inspection, the variations noted were enormous, (P = 0.000). On speciation of Candida in CHROM agar among the controls, PMD and OSCC groups, Candida albicans species was present in 9 (18%), 16 (32%), and 6 (12%), Candida krusei in 3 (6%), 6 (12%), and 13 (26%), Candida glabrata in 0, 0, and 8 (16%), and Candida tropicalis in 0, 0, and 3 (6%) cases, respectively. Nonetheless, only OSCC group reveal amalgamation of species such as C. glabrata and C. krusei was present in 2 (4%) case, C. tropicalis and C. krusei in was present 3 (6%) cases, C. tropicalis and C. glabrata was present in 2 (4%) case, C. albicans and C. tropicalis was present in 2 (4%) cases, and C. krusei, C. glabrata with C. albicans was present in 1 (2%) case, respectively. All other types of fungi were regarded as infectious excluding Candida, on analysis on SDA medium, infestation in the form of fungal molds was seen in 18 (36%) in controls, 12 (24%) in PMD and 8 (16%) in OSCC groups. CONCLUSION: We interpreted that the chief carrier of candidal species in PMDs and OSCC, yet more light is to be thrown on the topic that Candida has particular establishment in PMDs or in malignancy.

Evaluating the effectiveness of marine actinobacterial extract and its mediated titanium dioxide nanoparticles in the degradation of azo dyes.

Aim of the present study was to synthesize titanium dioxide nanoparticles (TiO2 NPs) from marine actinobacteria and to develop an eco-friendly azo-dye degradation method. A total of five actinobacterial isolates were isolated from Chennai marine sediments, Tamilnadu, India and analyzed for the synthesis of TiO2 NPs using titanium hydroxide. Among these, the isolate PSV 3 showed positive results for the synthesis of TiO2 NPs, which was confirmed by UV analysis. Further characterization of the synthesized TiO2 NPs was done using XRD, AFM and FT-IR analysis. Actinobacterial crude extract and synthesized TiO2 NPs was found efficient in degrading azo dye such as Acid Red 79 (AR-79) and Acid Red 80 (AR-80). Degradation percentage was found to be 81% for AR-79, 83% for AR-80 using actinobacterial crude extract and 84% for AR-79, 85% for AR-80 using TiO2 NPs. Immobilized actinobacterial cells showed 88% for AR-79 and 81% for AR-80, dye degrading capacity. Degraded components were characterized by FT-IR and GC-MS analysis. The phytotoxicity test with 500 µg/mL of untreated dye showed remarkable phenotypic as well as cellular damage to Tagetes erecta plant. Comparatively no such damage was observed on plants by degraded dye components. In biotoxicity assay, treated dyes showed less toxic effect as compared to the untreated dyes.

Protease inhibitors from marine actinobacteria as a potential source for antimalarial compound.

The study was planned to screen the marine actinobacterial extract for the protease inhibitor activity and its anti- Pf activity under in vitro and in vivo conditions. Out of 100 isolates, only 3 isolates exhibited moderate to high protease inhibitor activities on trypsin, chymotrypsin and proteinase K. Based on protease inhibitor activity 3 isolates were chosen for further studies. The potential isolate was characterized by polyphasic approach and identified as Streptomyces sp LK3 (JF710608). The lead compound was identified as peptide from Streptomyces sp LK3. The double-reciprocal plot displayed inhibition mode is non-competitive and it confirms the irreversible nature of protease inhibitor. The peptide from Streptomyces sp LK3 extract showed significant anti plasmodial activity (IC50: 25.78 µg/ml). In in vivo model, the highest level of parasitemia suppression (≈ 45%) was observed in 600 mg/kg of the peptide. These analyses revealed no significant changes were observed in the spleen and liver tissue during 8 dpi. The results confirmed up-regulation of TGF-ß and down regulation of TNF-α in tissue and serum level in PbA infected peptide treated mice compared to PbA infection. The results obtained infer that the peptide possesses anti- Pf activity activity. It suggests that the extracts have novel metabolites and could be considered as a potential source for drug development.

Streptomyces sp. LK3 mediated synthesis of silver nanoparticles and its biomedical application.

In the present study, the marine actinobacteria mediated biosynthesis of silver nanoparticles (AgNps) was achieved using Streptomyces sp LK3. The synthesized AgNps showed the characteristic absorption spectra in UV-vis at 420 nm, which confirmed the presence of nanoparticles. XRD analysis showed intense peaks at 2θ values of 27.51°, 31.87°, 45.57°, 56.56°, 66.26°, and 75.25° corresponding to (210), (113), (124), (240), (226), and (300) Bragg's reflection based on the fcc structure of AgNps. The FTIR spectra exhibited prominent peaks at 3,417 cm(-1) (OH stretching due to alcoholic group) and 1,578 cm(-1) (C=C ring stretching). TEM micrograph showed that the synthesized AgNps were spherical in shape with an average size of 5 nm. Surface morphology and topographical structure of the synthesized AgNps were dignified by AFM. The synthesized AgNps showed significant acaricidal activity against Rhipicephalus microplus and Haemaphysalis bispinosa with LC50 values of 16.10 and 16.45 mg/L, respectively. Our results clearly indicate that AgNps could provide a safer alternative to conventional acaricidal agents in the form of a topical antiparasitic formulation. The present study aimed to develop a novel, cost-effective, eco-friendly actinobacteria mediated synthesis of AgNps and its antiparasitic activity.

Crystal structure analysis of L-fuculose-1-phosphate aldolase from Thermus thermophilus HB8 and its catalytic action: as explained through in silico.

Fuculose phosphate aldolase catalyzes the reversible cleavage of fuculose-1-phosphate to dihydroxyacetone phosphate and L-lactaldehyde. A tetramer by nature, this enzyme from Thermus thermophilus HB8 represents the group of Class II aldolases. The structure was solved in two different space groups using the crystals obtained from slow evaporation vapour-diffusion and microbatch techniques. The detailed crystallization description has been reported previously. In this study, the structural features of fuculose phosphate aldolase from T. thermophilus have been explored extensively through sequence and structure comparisons with fuculose phosphate aldolases of different species. Finally, an in silico analysis using induced fit docking was attempted to deduce the binding mode of fuculose phosphate aldolase with its natural substrate fuculose-1-phosphate along with a substrate analog dihydroxyacetone phosphate and phosphoglycolohydroxymate--a potential aldolase inhibitor. The results show the mechanism of action may be similar to that of Escherichia coli fuculose aldolase.

Marine actinobacterial mediated gold nanoparticles synthesis and their antimalarial activity.

Streptomyces sp LK-3 (JF710608) mediated Gold nanoparticles (Au-N-LK3) were found within the size range of 5-50 nm. Au-N-LK3 treatment in Plasmodium berghei ANKA (PbA) infected mice delayed the parasitemia rise (~6%) compared to PbA infection on 8 days post infection. Survivability of mice increases to ~85% in Au-N-LK3 treated mice in contrast to in PbA (~50%) infected mice in 8 dpi with respect to control. During Au-N-LK3 treatment in PbA infection, histomorphological analysis revealed as such no change in spleen and liver tissue during 8 dpi. Our results confirmed up-regulation of TGF-ß and down-regulation of TNF-α in tissue and serum level in PbA infected Au-N-LK3 treated mice compared to PbA infection. No significant changes were found in the hatchability of Artemia embryos upto 8 mg. The results obtained suggest that the Au-N-LK3 possess anti-malarial activity and could be considered as a potential source for anti-malarial drug development. FROM THE CLINICAL EDITOR: These investigators present a method of marine actinobacteria mediated synthesis of gold nanoparticles, resulting in nanoparticles that possess anti-malarial activity and could be considered in future anti-malarial drug development.

Novel microbial route to synthesize ZnO nanoparticles using Aeromonas hydrophila and their activity against pathogenic bacteria and fungi.

In the present work, we describe a low-cost, unreported and simple procedure for biosynthesis of zinc oxide nanoparticles (ZnO NPs) using reproducible bacteria, Aeromonas hydrophila as eco-friendly reducing and capping agent. UV-vis spectroscopy, XRD, FTIR, AFM, NC-AFM and FESEM with EDX analyses were performed to ascertain the formation and characterization of ZnO NPs. The synthesized ZnO NPs were characterized by a peak at 374 nm in the UV-vis spectrum. XRD confirmed the crystalline nature of the nanoparticles and AFM showed the morphology of the nanoparticle to be spherical, oval with an average size of 57.72 nm. Synthesized ZnO NPs showed the XRD peaks at 31.75°, 34.37°, 47.60°, 56.52°, 66.02° and 75.16° were identified as (100), (002), (101), (102), (110), (112) and (202) reflections, respectively. Rietveld analysis to the X-ray data indicated that ZnO NPs have hexagonal unit cell at crystalline level. The size and topological structure of the ZnO NPs was measured by NC-AFM. The morphological characterization of synthesized nanoparticles was analyzed by FESEM and chemical composition by EDX. The antibacterial and antifungal activity was ended with corresponding well diffusion and minimum inhibitory concentration. The maximum zone of inhibition was observed in the ZnO NPs (25 µg/mL) against Pseudomonas aeruginosa (22±1.8 mm) and Aspergillus flavus (19±1.0 mm). Bacteria-mediated ZnO NPs were synthesized and proved to be a good novel antimicrobial material for the first time in this study.

Larvicidal, repellent, and ovicidal activity of marine actinobacteria extracts against Culex tritaeniorhynchus and Culex gelidus.

The purpose of the present study was to assess the effect of crude extracts of marine actinobacteria on larvicidal, repellent, and ovicidal activities against Culex tritaeniorhynchus and Culex gelidus (Diptera: Culicidae). The early fourth instar larvae of C. tritaeniorhynchus and C. gelidus, reared in the laboratory, were used for larvicidal, ovicidal, and repellent assay with crude extracts of actinobacteria. Saccharomonospora spp. (LK-1), Streptomyces roseiscleroticus (LK-2), and Streptomyces gedanensis (LK-3) were identified as potential biocide producers. Based on the antimicrobial activity, three strains were chosen for larvicidal activity. The marine actinobacterial extracts showed moderate to high larvicidal effects after 24 h of exposure at 1,000 ppm and the highest larval mortality was found in extract of LK-3 (LC(50) = 108.08 ppm and LC(90) = 609.15 ppm) against the larvae of C. gelidus and (LC(50) = 146.24 ppm and LC(90) = 762.69 ppm) against the larvae of C. tritaeniorhynchus. Complete protections for 240 min were found in crude extract of LK-2 and LK-3 at 1,000 ppm, against mosquito bites of C. tritaeniorhynchus and C. gelidus, respectively. After 24-h treatment, mean percent hatchability of the ovicidal activity was observed. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. Crude extracts of LK-1 and LK-3 showed no hatchability at 1,000 ppm against C. tritaeniorhynchus and C. gelidus, respectively. This is an ideal ecofriendly approach for the control of Japanese encephalitis vectors, C. tritaeniorhynchus and C. gelidus.