Disappearance of "Elongated Pony Tail Sign" Following Chemoradiotherapy in a Case of Primary Cerebellopontine Angle Ependymoma With Spinal Drop Metastasis: 18 F-FDG PET/CT Scan Findings.

ABSTRACT: Ependymomas are rare glial tumors that commonly arise from the lining cells of ventricular system and constitute ~10% of intracranial pediatric malignancies. The incidence of ependymoma in adults is rare. Due to close approximation with the ventricular system, subtentorial ependymomas are more prone to show cerebrospinal fluid metastasis compared with supratentorial ependymomas. We present a case of subtentorial cerebellopontine angle ependymoma with diffuse spinal drop metastases showing "elongated pony tail appearance" in a 69-year-old man with complete metabolic response on 18 F-FDG PET/CT imaging following chemoradiotherapy.

Systematic review and meta-analysis of studies comparing baseline D-dimer level in stroke patients with or without cancer: Strength of current evidence.

Objectives: D-dimer levels are increased in stroke and cancer. Cancer patients are at a higher risk of stroke. However, the evidence is unclear if high D-dimer in stroke patients can suggest the diagnosis of concomitant cancer or the development of stroke in a cancer patient. The objective is to assess the evidence available on the baseline D-dimer level in stroke patients with and without cancer. Materials and Methods: We conducted the systematic review and meta-analysis using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched PUBMED, Cochrane, ScienceDirect, and Scopus for potentially eligible articles published till June 2023. All the review steps were iterative and done independently by two reviewers. The Newcastle-Ottawa scale tool was used to assess the quality of included studies for case control and cohort studies and the Agency for Healthcare Research and Quality tool for cross-sectional studies. The qualitative synthesis is presented narratively, and quantitative synthesis is shown in the forest plot using the random effects model. I2 of more than 60% was considered as high heterogeneity. Results: The searches from all the databases yielded 495 articles. After the study selection process, six papers were found eligible for inclusion in the qualitative and quantitative synthesis. In the present systematic review, 2651 patients with ischemic infarcts are included of which 404 (13.97%) patients had active cancer while 2247 (86.02%) did not. The studies included were of high quality and low risk of bias. There were significantly higher baseline D-dimer levels in stroke patients with cancer than in non-cancer patients with a mean difference of 4.84 (3.07-6.60) P < 0.00001. Conclusion: D-dimer is a simple and relatively non-expensive biomarker that is increased to significant levels in stroke patients, who have cancer and therefore may be a tool to predict through screening for active or occult cancer in stroke patients.

Antimicrobial resistance landscape in a metropolitan city context using open drain wastewater-based metagenomic analysis.

One Health concept recognizes the inextricable interactions of diverse ecosystems and their subsequent effect on human, animal and plant health. Antimicrobial resistance (AMR) is a major One Health concern and is predicted to cause catastrophes if appropriate measures are not implemented. To understand the AMR landscape in a south Indian metropolitan city, metagenomic analysis of open drains was performed. The data suggests that in January 2022, macrolide class of antibiotics contributed the highest resistance of 40.1% in the city, followed by aminoglycoside- 24.4%, tetracycline- 11.3% and lincosamide- 6.7%. The 'mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics' were the major contributor of resistance with a prevalence of 39.7%, followed by '16s rRNA with mutation conferring resistance to aminoglycoside antibiotics'- 22.2%, '16S rRNA with mutation conferring resistance to tetracycline derivatives'- 9.2%, and '23S rRNA with mutation conferring resistance to lincosamide antibiotics'- 6.7%. The most prevalent antimicrobial resistance gene (ARG) 'mutations in the 23S rRNA gene conferring resistance to macrolide antibiotics' was present in multiple pathogens including Escherichia coli, Campylobacter jejuni, Acinetobacter baumannii, Streptococcus pneumoniae, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Klebsiella pneumoniae and Helicobacter pylori. Most of the geographical locations in the city showed a similar landscape for AMR. Considering human mobility and anthropogenic activities, such an AMR landscape could be common across other regions too. The data indicates that pathogens are evolving and acquiring antibiotic resistance genes to evade antibiotics of multiple major drug classes in diverse hosts. The outcomes of the study are relevant not only in understanding the resistance landscape at a broader level but are also important for identifying the resistant drug classes, the mechanisms of gaining resistance and for developing new drugs that target specific pathways. This kind of surveillance protocol can be extended to regions in other developing countries to assess and combat the problem of antimicrobial resistance.

Analysis of traumatic intracranial hemorrhage and delayed traumatic intracranial hemorrhage in patients with isolated head injury on anticoagulation and antiplatelet therapy.

Objectives: Anticoagulants and antiplatelet (ACAP) agents are increasingly and frequently used, especially in the elderly. The present study was carried out to assess the prevalence of delayed traumatic intracranial hemorrhage (dtICH) after a normal result on an initial head computed tomography (CT) in adults who were taking ACAP medication. Materials and Methods: The present retrospective included all adult patients who arrived in the emergency department between January 2017 and January 2021 with a history of fall from the patient's own height, while being on ACAP medication with an isolated head injury. The Institutional Review Board approved the study with a waiver of consent. The primary outcome measures were prevalence of dtICH in patients who had initial normal CT scan brain and were on ACAP medication. Results: There were 2137 patients on ACAP medication, of which 1062 were male, and 1075 were of the female gender. The mean age of the patients was 82.1 years. About 8.2% had positive first CT scans (176/2137), while 0.023 (27/1149) had dtICH. The most common positive finding on the CT scan was subarachnoid hemorrhage followed by subdural hemorrhage. Male gender positively correlated with increased risk for first CT being positive (P = 0.033). Patient's with comorbidity of cirrhosis and chemotherapy had higher risk of dtICH (P = 0.47, 0.011). Conclusion: There was a very low (0.023%) prevalence of dtICH. Dual therapy or Coumadin therapy made up the majority of tICH. Cirrhosis and chemotherapy were associated with the risk of a repeat CT scan being positive with an initial CT scan negative.

Enzyme targeted delivery of sivelestat loaded nanomicelle inhibits arthritic severity in experimental arthritis.

AIMS: Rheumatoid arthritis (RA) is chronic inflammatory disorder mainly affects the lining of articular cartilage of synovial joints characterized by severe inflammation and joint damage. The expression of proteolytic enzymes like MMP-2 and Neutrophil Elastase (NE) worsens the RA condition. To address this concern, we have synthesized dual enzyme targeted chlorotoxin conjugated nanomicelles loaded with sivelestat as broad spectrum treatment for RA. MATERIALS AND METHODS: Conjugation of the chlorotoxin over nanomicelle and incorporation of sivelestat in nanomicelle provide it dual targeting potential. The sivelestat loaded nanomicelle (SLM) evaluated for the drug release and in-vitro cytocompatibility. Further, investigated its in-vivo anti-arthritic potential on collagen-induced arthritis in wistar rats. KEY FINDINGS: The microscopic observation of SLM showed spherical ball like appearance with size ranging from 190 to 230 nm. SLM showed good drug loading and encapsulation efficiency along with no cytotoxicity against healthy cell lines. In-vivo therapeutic assessment on collagen induced arthritis rat model showed potential chondroprotection. The microscopic visualization of articular cartilage by staining showed that it restores the cartilage integrity and lowers the expression of pro-inflammatory enzymes showed by Immunohistochemistry and Immunofluorescence. We observed that, it restrain the mediators of synovial inflammation by simultaneous inhibition of the proteolytic enzymes involved in swelling, cartilage destruction and joint damage which provides strong chondroprotection. SIGNIFICANCE: We report that significant alleviation of inflammation and inhibition of proteolytic enzymes together might provide enhanced potential for the treatment and management of RA.

Highly Biocompatible Smart Injectable Hydrogel for the Management of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that severely affects joints and restricts locomotion. Various treatment regimens are available for RA, providing short-term relief from pain, but long-term relief from the disease is still not available. Evidently, cytokines play a crucial role in the pathophysiology of the disease. However, aberrant immune responses, genetic dispositions, viral infections, or toxicants are some possible causative mediators of RA. The synovial fluid of rheumatoid arthritis patients encompass cytokines, especially osteoclastogenic cytokines, and invasion factors such as macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL). Moreover, tumor necrosis factor-α (TNF-α) and interleukins (IL-1, 6, and 17) intensify osteoclast differentiation and activation. Therefore, in order to restrict the cytokine expression, we used budesonide as a therapeutic lead and encapsulated it into a highly biocompatible hydrogel system. The hydrogel system developed by us is enzyme-responsive and provides sustained drug release flow over an extended period of time. This hydrogel is characterized by ζ-potential analysis, field-emission scanning electron microscopy (FE-SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and it is further encapsulated with budesonide (glucocorticoids) for therapeutic purposes. Evidently, Bud-loaded ER-hydrogel showed improvement in joint physiology compared to the disease group and downregulated the inflammatory markers.

Colon-Adhering Delivery System with Inflammation Responsiveness for Localized Therapy of Experimental Colitis.

Ulcerative colitis (UC) is a chronic inflammation-related disease that severely affects the colon and rectum regions. A variety of therapy regimens are used for the treatment of UC. Clinically, therapeutic enema is the choice of therapy for UC patients. Irrespective of on-site administration, the major limitation of therapeutic enemas is the dispossession of the medicine followed by low drug availability for the therapeutic action. In our present work, we have developed an enzyme-responsive injectable hydrogel (ER-hydrogel) to overcome the limitations of therapeutic enema. The hydrogels possess two major advantages, which are being exploited for therapeutic drug delivery in UC: prolonged retention and enzyme responsiveness. The former is one of the prominent advantages of hydrogel compared to free drug enema and the latter controls the release of the drug or provides drug release on-demand. The ER-hydrogel was formulated by the heat-cool method and for therapeutic purposes, a corticosteroid drug, budesonide (Bud), was encapsulated into the ER-hydrogel and evaluated for its various physicochemical and therapeutic potentials in dextran sodium sulfate (DSS)-induced UC. In vitro and ex vivo adhesion studies confirm the retention or mucoadhesive nature of the ER-hydrogel, and the upsurge in Bud release from the Bud-loaded ER-hydrogel upon the addition of esterase enzyme confirms the enzyme-mediated drug release from the ER-hydrogel. Moreover, Bud-loaded ER-hydrogel exhibited promising results in alleviating the disease activity index of UC, and restored the length of the colon, which is the main hallmark of UC. In terms of the health of the colon tissue, the Bud-loaded ER-hydrogel restored the colonic tissue damage, as seen in the H&E-stained, AB-NR-stained, and HID-AB-stained colon sections. Finally, the Bud-loaded ER-hydrogel also markedly subsided the IL-1ß, TNF-α, MPO, and nitrite levels in serum and colon tissues. Thus, the fabricated Bud-loaded ER-hydrogel possesses appreciable translational potential due to its ability to significantly ameliorate inflammatory changes compared to naive or water-based therapeutic enema in acute experimental colitis in mice.

Prognostic factors affecting outcome of multifocal or multicentric glioblastoma: A scoping review.

It has been reported that patients with multiple lesions have shorter overall survival compared to single lesion in glioblastoma (GBM). Number of lesions can profoundly impact the prognosis and treatment outcome in GBM. In view of the advancement of imaging, multiple GBM (mGBM) lesions are increasingly recognized and reported. The scoping review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension statement for systematic review. Database was searched to collect relevant articles based on predefined eligibility criteria. Our observations suggest that multifocal/multicentric GBM has poorer outcome compared to GBM with singular lesion (sGBM). As the factors influencing the prognosis and outcome is poorly understood and there is no consensus in the existing literature, this review is clinically relevant. As patients with single lesion are more likely to undergo gross total excision, it is likely that further adjuvant treatment may be decided by extent of resection. This review will be helpful for design of further prospective randomized studies for optimal management of mGBM.

Cortisone-loaded stearoyl ascorbic acid based nanostructured lipid carriers alleviate inflammatory changes in DSS-induced colitis.

Ulcerative colitis is a chronic inflammatory disease which poorly affects the colon and spreads toward the rectum over time. Cortisone (CRT) is a corticosteroid clinically used for the management of inflammatory diseases like colitis and other inflammatory bowel diseases. Due to some physicochemical properties' cortisone has limited potency in clinics. To overcome drug-related problems, we successfully prepared lipid nanocarriers with generally regarded as safe (GRAS) materials approved by USFDA. The present study aimed to assess the therapeutic efficacy of CRT-loaded 6-o-stearoyl ascorbic acid (SAA) nanostructured lipid carriers (NLCs) against DSS-induced colitis mice. Formulation and characterizations of reported nanostructured lipid carrier were performed according to our previously optimized parameters. The average hydrodynamic diameter of NLCs was 182 nm as measured by DLS with 81.14 % encapsulation efficacy. TEM, AFM and SEM images analysis confirmed its spherical appearance. hTERT-BJ cells viability up to a dose of 500 µg/ml shows cytocompatible characteristics of blank NLCs. CRT-loaded NLCs treatment normalizes physically observed parameters such as disease activity index, weight variation etc. These NLCs were able to significantly reduce the severity of colitis in terms of colon histoarchitecture, regaining of the goblet cells, mucins secretions, inhibition of proinflammatory cytokines etc. Treatment with CRT-loaded NLCs effectively downregulated the overexpression of inflammatory enzymes like cyclooxygenase-2 (COX-2), Inducible nitric oxide synthase (iNOS) etc. The results of this study concluded that these CRT-encapsulated NLCs efficiently manage the disease severity induced by DSS.

Caffeic Acid-Conjugated Budesonide-Loaded Nanomicelle Attenuates Inflammation in Experimental Colitis.

Ulcerative colitis is a multifactorial disease of the gastrointestinal tract which is caused due to chronic inflammation in the colon; it usually starts from the lower end of the colon and may spread to other portions of the large intestine, if left unmanaged. Budesonide (BUD) is a synthetically available second-generation corticosteroidal drug with potent local anti-inflammatory activity. The pharmacokinetic properties, such as extensive first-pass metabolism and quite limited bioavailability, reduce its therapeutic efficacy. To overcome the limitations, nanosized micelles were developed in this study by conjugating stearic acid with caffeic acid to make an amphiphilic compound. The aim of the present study was to evaluate the pharmacological potential of BUD-loaded micelles in a mouse model of dextran sulfate sodium-induced colitis. Micelles were formulated by the solvent evaporation method, and their physicochemical characterizations show their spherical shape under microscopic techniques like atomic force microscopy, transmission electron microscopy, and scanning electron microscopy. The in vitro release experiment shows sustained release behavior in physiological media. These micelles show cytocompatible behavior against hTERT-BJ cells up to 500 µg/mL dose, evidenced by more than 85% viable cells. BUD-loaded micelles successfully normalized the disease activity index and physical observation of colon length. The treatment with BUD-loaded micelles alleviates the colitis severity as analyzed in histopathology and efficiently, overcoming the disease severity via downregulation of various related cytokines (MPO, NO, and TNF-α) and inflammatory enzymes such as COX-2 and iNOS. Results of the study suggest that BUD-loaded nano-sized micelles effectively attenuate the disease conditions in colitis.

Structural and developmental dynamics of Matrix associated regions in Drosophila melanogaster genome.

BACKGROUND: Eukaryotic genome is compartmentalized into structural and functional domains. One of the concepts of higher order organization of chromatin posits that the DNA is organized in constrained loops that behave as independent functional domains. Nuclear Matrix (NuMat), a ribo-proteinaceous nucleoskeleton, provides the structural basis for this organization. DNA sequences located at base of the loops are known as the Matrix Attachment Regions (MARs). NuMat relates to multiple nuclear processes and is partly cell type specific in composition. It is a biochemically defined structure and several protocols have been used to isolate the NuMat where some of the steps have been critically evaluated. These sequences play an important role in genomic organization it is imperative to know their dynamics during development and differentiation. RESULTS: Here we look into the dynamics of MARs when the preparation process is varied and during embryonic development of D. melanogaster. A subset of MARs termed as "Core-MARs" present abundantly in pericentromeric heterochromatin, are constant unalterable anchor points as they associate with NuMat through embryonic development and are independent of the isolation procedure. Euchromatic MARs are dynamic and reflect the transcriptomic profile of the cell. New MARs are generated by nuclear stabilization, and during development, mostly at paused RNA polymerase II promoters. Paused Pol II MARs depend on RNA transcripts for NuMat association. CONCLUSIONS: Our data reveals the role of MARs in functionally dynamic nucleus and contributes to the current understanding of nuclear architecture in genomic context.

Bioengineered and functionalized silk proteins accelerate wound healing in rat and human dermal fibroblasts.

Wound healing is an intrinsic process directed towards the restoration of damaged or lost tissue. The development of a dressing material having the ability to control the multiple aspects of the wound environment would be an ideal strategy to improve wound healing. Though natural silk proteins, fibroin, and sericin have demonstrated tissue regenerative properties, the efficacy of bioengineered silk proteins on wound healing is seldom assessed. Furthermore, silk proteins sans contaminants, having low molecular masses, and combining with other bioactive factors can hasten the wound healing process. Herein, recombinant silk proteins, fibroin and sericin, and their fusions with cecropin B were evaluated for their wound-healing effects using in vivo rat model. The recombinant silk proteins demonstrated accelerated wound closure in comparison to untreated wounds and treatment with Povidone. Among all groups, the treatment with recombinant sericin-cecropin B (RSC) showed significantly faster healing, greater than 90% wound closure by Day 12 followed by recombinant fibroin-cecropin B (RFC) (88.86%). Furthermore, histological analysis and estimation of hydroxyproline showed complete epithelialization, neovascularization, and collagenisation in groups treated with recombinant silk proteins. The wound healing activity was further verified by in vitro scratch assay using HADF cells, where the recombinant silk proteins induced cell proliferation and cell migration to the wound area. Additionally, wound healing-related gene expression showed recombinant silk proteins stimulated the upregulation of EGF and VEGF and regulated the expression of TGF-ß1 and TGF-ß3. Our results demonstrated the enhanced healing effects of the recombinant silk fusion proteins in facilitating complete tissue regeneration with scar-free healing. Therefore, the recombinant silks and their fusion proteins have great potential to be developed as smart bandages for wound healing.

An investigation into the effects of infection and ORF expression patterns of the Indian bidensovirus isolate (BmBDV) infecting the silkworm Bombyx mori.

The Indian isolate of Bombyx mori bidensovirus (BmBDV) is a bipartite virus that comprises of a segmented, non-homologous, two linear single-strands of DNA molecules (VD1 and VD2). It is one of the causative agents of the fatal silkworm disease 'Flacherie' that causes severe crop loss for the sericulture farmers. Genome analyses of the Indian isolate of BmBDV revealed that it consists of 6 putative ORFs similar to the Japanese and Chinese isolates. VD1 consists of 4 ORFs while VD2 has 2 ORFs that code for 4 non- structural (NS) and 2 structural (VP) proteins, in total. In this study, we investigated, in detail, the impact of BmBDV pathogenesis on growth and development of the silkworm Bombyx mori, at different developmental stages. Mortality rate and weight uptake analyses were also performed on newly ecdysed 4th instar larvae. BmBDV infection was not found to be developmental stage specific and it occurred at all stages. Onset of mortality took place 8 days post infection (dpi) and 100% mortality occurred at 11 dpi. The infected larvae showed a significant difference in weight uptake wherein from 7 dpi the larvae stopped gaining weight and from 8th dpi started demonstrating the typical symptoms of flacherie. Further, the expression pattern of the 6 viral ORFs were also investigated in the newly ecdysed 4th instar BmBDV infected silkworms. Among all the six ORFs, VD2 ORF 1 and 2 revealed the highest transcript numbers, which was followed by VD1 ORF 4 that encodes for the viral DNA polymerase enzyme. This was the first ever attempt to understand the pathogenesis and the expression pattern of all the six ORF transcripts of the Indian isolate of BmBDV.

Thiol-Functionalized Cellulose-Grafted Copper Oxide Nanoparticles for the Therapy of Experimental Colitis in Swiss Albino Mice.

Ulcerative colitis (UC) is a chronic inflammatory disease, which deleteriously affects the lower end of the gastrointestinal tract, i.e., the colon and the rectum. UC affects colonic inflammatory homeostasis and disrupts intestinal barrier functions. Intestinal tissue damage activates the immune system and collectively worsens the disease condition via the production of various cytokines. Ongoing therapeutics of UC have marked limitations like rapid clearance, extensive first-pass metabolism, poor drug absorption, very low solubility, bioavailability, etc. Because of these restrictions, the management of UC demands a rational approach that selectively delivers the drug at the site of action to overcome the therapeutic limiting factors. Metallic nanoparticles (NPs) have good therapeutic efficacy against colitis, but their uses are limited due to adverse effects on the biological system. In this study, we have used biocompatible thiol-functionalized cellulose-grafted copper oxide nanoparticles (C-CuI/IIO NPs) to treat UC. The metal NPs alleviated the colitis condition as evidenced by the colon length and observed physical parameters. Analysis of histopathology demonstrated the recovery of the colon architecture damaged by dextran sulfate sodium-induced colitis. Treatment with C-CuI/IIO NPs reduced the disintegration of goblet cells and the retainment of sulfomucin. Significant downregulation of inflammatory markers like MPO activity, as well as levels of nitrite and TNF-α, was found following C-CuI/IIO NP treatment. The observations from the study suggested that intrarectal treatment of colitis with cellulose-based C-CuI/IIO NPs successfully combated the intestinal inflammatory condition.

Transgenic Silkworms Overexpressing Relish and Expressing Drosomycin Confer Enhanced Immunity to Multiple Pathogens.

The sericulture industry faces substantial economic losses due to severe pathogenic infections caused by fungi, viruses, and bacteria. The development of transgenic silkworms against specific pathogens has been shown to enhance disease resistance against a particular infection. A single gene or its products that can confer protection against multiple pathogens is required. In an attempt to develop silkworms with enhanced immunity against multiple pathogens, we generated transgenic silkworm lines with an overexpressed NF-kB transcription factor, Relish 1, under two different promoters. Separately, a potent anti-fungal gene, Drosomycin, was also expressed in transgenic silkworms. Both Relish 1 and Drosomycin transgenic silkworms had single copy genomic integration, and their mRNA expression levels were highly increased after infection with silkworm pathogens. The overexpression of the Relish 1 in transgenic silkworms resulted in the upregulation of several defense-related genes, Cecropin B, Attacin, and Lebocin, and showed enhanced resistance to Nosema bombycis (microsporidian fungus), Nucleopolyhedrovirus (BmNPV), and bacteria. The Drosomycin expressing transgenic silkworms showed elevated resistance to N. bombycis and bacteria. These findings demonstrate the role of Relish 1 in long-lasting protection against multiple pathogens in silkworms. Further, the successful introduction of a foreign gene, Drosomycin, also led to improved disease resistance in silkworms.

Nanotechnology-Assisted, Single-Chromophore-Based White-Light-Emitting Organic Materials with Bioimaging Properties.

White-light-emitting (WLE) organic materials, especially small molecules comprising a single chromophoric unit, have received much attention due to their tremendous use in modern-day electronic devices and biomaterials. They can increase the efficiency and lifetime of devices compared to the currently used combination approach. Herein, we explored a small symmetric push-pull organic molecule Hexyl-TCBD with a single 1,1,4,4-tetracyanobuta-1,3-diene (TCBD) chromophoric unit containing urea as a key functional group on an acceptor-donor∼donor-acceptor (A-D∼D-A) backbone for its ability to show white-light emission in solution as well as in the solid state. The luminescence was absent in the solid state due to the H-bonding- and π-stacking-driven quenching processes, while emission behavior in solution was tunable with variable CIE chromaticity index values via hydrogen (H)-bonding-governed disaggregation phenomena. Translation of WLE from the Hexyl-TCBD solution to a solid state was demonstrated by utilizing nonemissive polystyrene (80 wt % with respect to the chromophore) as the matrix to obtain WLE nanofibers (made by the electrospun technique) via segregating the molecules. The optical microscopy study validated the WLE nanofibers. The presence of multicolor photoluminescence, including white light, could be fine-tuned through various excitation wavelengths, solvent polarities, and polystyrene matrices. Furthermore, the detailed photophysical studies, including lifetime measurements, indicated that the inherent intramolecular charge transfer (ICT) bands of Hexyl-TCBD exhibit better ICT state stabilization by space charge distribution through the modulation of H-bonding between urea groups. Finally, a cytotoxicity study was performed for Hexyl-TCBD on normal and cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to explore bioimaging applications in biosystems. MTT results revealed significant toxicity toward cancer cells, whereas normal cells exhibited good biocompatibility.

Antitumor drugs effect on the stability of double-stranded DNA: steered molecular dynamics analysis.

Denaturation of the DNA double helix inside the cell is essential for cellular processes such as replication and transcription for the growth of the cells. However, the growth of unwanted cells, which are responsible for cancerous kind of disease, is one of the biggest challenges of modern therapeutics. DNA cross-linking agents may kill cancer cells by damaging their DNA and stopping them from dividing. In the present study, we have carried out steered molecular dynamics simulations to study the effects of rupture and unzipping forces on the stability of dsDNA in the absence and presence of covalently bonded drugs. We have found that the stability of dsDNA increases strongly in the presence of covalently bonded drugs. The microscopic study of disruption of hydrogen-bonds associated with base-pairs of the dsDNA and the study of the variation of stacking overlap parameters gives evidence of symmetry during the rupture and asymmetry in the unzip event. The significance of the mechanism of force-induced melting study of the dsDNA in the absence and presence of antitumor drugs might have a biological relevance as it provides a pathway to open the double helix in a specific position and may help for the pharmaceutical design of drugs.Communicated by Ramaswamy H. Sarma.

Nanotized kinetin enhances essential oil yield and active constituents of mint via improvement in physiological attributes.

Often mint (Mentha arvensis L.) faces unforeseen limitations, resulting in a low yield and quality of essential oil (EO), especially menthol content necessitating the need to explore the potential of modern technology to overcome this predicament. One of such techniques is the use of nanomaterials. The bulk (un-nanotized) form of PGRs (plant growth regulators) has been considered as a potential tool for crop improvement. Utilizing the top-down approach of nanotization, bulk PGR kinetin was ball-milled to the nano-scale range. A pot experiment was conducted on mint applying bulk- and nano-kinetin through foliar application. The concentrations of spray-treatments included 0 (de-ionized water, control), 10, 20, and 30 µM of bulk-as well as nanotized-kinetin. Both forms of kinetin manifested their patterns in the plant. Treatment N2 (20 µM of nanotized-kinetin) excelled in all other treatments for most of the parameters studied. As compared with De-ionized water-spray control, it resulted in the highest improvement in photosynthetic efficiency, Carbonic anhydrase activity, EO content (46.6 %), EO yield (50.8 %), and density as well as the diameter of PGTs (peltate glandular trichomes). Treatment N2, equalled by treatment B2 (20 µM of bulk-kinetin), maximally improved the menthol yield. The highest content and yield of EO, as a result of N2 application, was attributed to its manifestation in terms of the improved photosynthetic machinery, enzyme activity, and vigour (density and diameter) of PGTs. Since treatment N2 increased the most desirable EO-traits, viz. content and yield of EO along with yield of menthol, it might be recommended for successful production of mint.