A non-B DNA binding peptidomimetic channel alters cellular functions.

DNA binding transcription factors possess the ability to interact with lipid membranes to construct ion-permeable pathways. Herein, we present a thiazole-based DNA binding peptide mimic TBP2, which forms transmembrane ion channels, impacting cellular ion concentration and consequently stabilizing G-quadruplex DNA structures. TBP2 self-assembles into nanostructures, e.g., vesicles and nanofibers and facilitates the transportation of Na+ and K+ across lipid membranes with high conductance (~0.6 nS). Moreover, TBP2 exhibits increased fluorescence when incorporated into the membrane or in cellular nuclei. Monomeric TBP2 can enter the lipid membrane and localize to the nuclei of cancer cells. The coordinated process of time-dependent membrane or nuclear localization of TBP2, combined with elevated intracellular cation levels and direct G-quadruplex (G4) interaction, synergistically promotes formation and stability of G4 structures, triggering cancer cell death. This study introduces a platform to mimic and control intricate biological functions, leading to the discovery of innovative therapeutic approaches.

Effect of irradiated nonionic surfactant on drug-protein binding.

In this work, the effect of γ-irradiated surfactants on drug-protein binding has been assessed. Irradiated aqueous solutions of Pluronic F-127, Pluronic L-35, Tween 20, and Tween 80 surfactants were used. Gamma irradiation was carried out for three different doses, to these four surfactants viz., 6, 30, and 36 kGy. Two drugs, Ornidazole (ONZ) and Telmisartan (TMS) were used for the binding study. The effect of four irradiated surfactants in the presence of drug - Bovine serum albumin (BSA) protein was analyzed. The drug solutions in methanol-aqueous media were combined with BSA in the initial step. In the next two succeeding steps, drug-BSA interaction in the presence of unirradiated and irradiated surfactants were carried out. The results of drug-BSA due to addition of irradiated and unirradiated surfactants were compared. The interaction processes were assessed through UV Spectroscopy, DLS, zeta potential, turbidity, and docking studies. Improved binding was observed for both the drugs and four surfactants for irradiated surfactants as determined from the binding constant values using UV spectroscopic studies. The DLS measurements demonstrated no general trend of increase or decrease in micellar size with absorbed dose. The binding and change in the size of micelles were observed to be highly drug and surfactant-specific. Among the four surfactants, irradiated Pluronic F-127 showed higher binding affinity. To the best of our knowledge, this is the first report on the effect of γ-irradiated surfactant on drug-BSA interaction. This can be applied to other drug-protein systems to tune their interaction to the required level.Communicated by Ramaswamy H. Sarma.

Synergistic adsorption and photocatalytic degradation of tetracycline using a Z-scheme kaolin/g-C3N4/MoO3 nanocomposite: A sustainable approach for water treatment.

This research focuses on the synthesis and application of a novel kaolin-supported g-C3N4/MoO3 nanocomposite for the degradation of tetracycline, an important antibiotic contaminant in water systems. The nanocomposite was prepared through a facile and environmentally friendly approach, leveraging the adsorption and photocatalytic properties of kaolin, g-C3N4 and MoO3 nanoparticles, respectively. Comprehensive characterization of the nanocomposite was conducted using techniques such as X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR) and optical spectra. The surface parameters were studied using N2 adsorption-desorption isotherm. The elemental composition was studied using X-ray photoelectron spectroscopy. The efficiency of the developed nanocomposite in tetracycline degradation was evaluated and the results revealed an efficient tetracycline degradation exhibiting the synergistic effects of adsorption and photocatalytic degradation in the removal process. The tetracycline degradation was achieved in 60 min. Kinetic studies and thermodynamic analyses provided insights into the degradation mechanism, suggesting potential applications for the nanocomposite in wastewater treatment. Additionally, the recyclability and stability of the nanocomposite were investigated, demonstrating its potential for sustainable and long-term application in water treatment.

pH-dependent complex formation with TAR RNA and DNA: application towards logic gates.

Nucleic acid-based logic gates have shown great potential in biotechnology, medicine as well as diagnostics. Herein, we have constructed pH-responsive logic devices by utilizing HIV-1 TAR hairpins in combination with a thiazole peptide that exhibits turn-on fluorescence upon interacting with TAR RNA or DNA. Based on this, INHIBIT-AND and YES-INHIBIT-AND logic gates were constructed in parallel. The pH alteration leads to conformational changes of the hairpin structure, enabling the construction of a multi-reset reusable logic system which could be developed for in vitro sensing of the HIV-1 viral RNA.

Anterior segment optical coherence tomography characteristics and management of a unique spectrum of foreign bodies in the cornea and anterior chamber.

Purpose: To report anterior-segment optical coherence tomography (ASOCT) characteristics of different types of corneal and anterior chamber (AC) foreign bodies (FBs) and their usefulness in diagnosis and management. Methods: This is a retrospective descriptive clinical study involving 11 eyes of 11 patients who presented at the outpatient department of a tertiary ophthalmic care center from January 2017 to January 2022. All patients had a diagnosed or suspected corneal FB. All participants underwent a comprehensive ophthalmological examination, followed by slit-lamp photography and ASOCT. FB removal was done where required by an external, internal, or combined approach. Results: The mean age of patients was 28.2 (7-53) years. Ten were male, and one was female. Seven patients had a definitive positive history of injury; in one, there was a history suggestive of trauma, one had the post-operative complication of scleral buckling surgery, and two patients had a history of insect fall in the eyes. Three patients had acute, four had sub-acute, and four had chronic presentations. Descemet's membrane (DM) breach was suspected in three cases of deep FB, which was later confirmed on ASOCT. In two cases, DM was presumed to be intact clinically, but ASOCT showed an AC penetration. The FB was removed in seven patients, one via slit-lamp, one via an external approach, two via an internal approach, and three via a combined approach. Conclusion: ASOCT facilitates non-invasive rapid imaging of ocular tissue at various depths, provides an accurate assessment of FB characteristics, and thereby serves as an additional tool in our armamentarium for diagnosis and management of deep corneal and AC FBs.

Vertical scan imaging of Anterior Segment Optical Coherence Tomography for descemet anchoring caterpillar seta: A case report and review of literature.

Purpose: To report Anterior Segment Optical Coherence Tomography (ASOCT) characteristic and its usefulness in the case of Descemet's membrane (DM) anchoring caterpillar seta, highlighting the importance of vertical scans of ASOCT in detecting and delineating the deep seta and its anterior chamber (AC) penetration. Observation: A 30-year-old male patient presented with complaints of foreign body sensation and watering in the left eye after falling of an insect. Slit-lamp examination showed the presence of two caterpillar hairs, one embedded in the superficial conjunctiva and the second one embedded in the corneal stroma. Conjunctival hair was removed leading to the resolution of symptoms. ASOCT was done for deep corneal hair which showed DM breach and AC protrusion in volume vertical scans. ASOCT scan on follow-up visit showed migration of seta in AC. Deep seta being inert was not removed and the patient was closely followed. Conclusion: and IMPORTANCE: To the best of our knowledge, this is the first case reporting vertical scan imaging of caterpillar seta and showing AC migration of seta on ASOCT.

Reticular epithelial corneal edema as a novel side-effect of Rho Kinase Inhibitors: An Indian scenario.

Purpose: To describe clinical course, characteristics, and outcome of reticular epithelial corneal edema (RECE) occurring as a not-so-infrequent adverse effect of a novel drug, Rho-kinase inhibitors (ROCK-I)- netarsudil (0.02%) and ripasudil (0.4%). Methods: This was a retrospective observational non-randomized study. In this study, 12 eyes of 11 patients presenting at a tertiary eye care center between April 2021 and September 2021 were included. All 12 eyes developed a distinctive honeycomb pattern of RECE after starting topical ROCK-I. All patients were subjected to detailed ophthalmic examinations. Results: Eight patients were started on netarsudil (0.02%) and three on ripasudil (0.4%). Five eyes had a prior history of corneal edema. The remaining seven had the presence of ocular comorbidities predisposing to corneal edema. The average time for RECE occurrence was 25 days for netarsudil and 82 days for ripasudil. Visual acuity decreased in two eyes, remained unaffected in four eyes, and could not be quantified in four eyes due to preexisting profound visual impairment. Five eyes had symptoms of ocular surface discomfort associated with bullae. Symptoms and bullae resolved in all eyes in whom ROCK-I was stopped. The average time to resolution of RECE was 10 days for netarsudil and 25 days for ripasudil. Conclusion: RECE after ROCK-I occurs with the use of both netarsudil and ripasudil, although the characteristics differ. The presence of corneal edema and endothelial decompensation seem to be a risk factor, and cautious use is warranted in these patients. Four clinical stages of RECE are described. ROCK-I act as a double-edged sword in patients with endothelial decompensation. Large-scale studies are required to know the exact incidence, pathophysiology, and long-term consequences of the aforementioned side-effect.

Bioactive platinum complex of ligand bearing pyrimidine skeleton: DNA/BSA binding, molecular docking, anticancer, antioxidant and antimicrobial activities.

A new octahedral platinum complex [PtLCl4] of Schiff base ligand containing pyrimidine and morpholine skeleton (where, L is 4,6-dichloropyrimidin-5-yl)methylene)-2-morpholinoethanamine) was isolated and characterized by elemental analysis, 1H-NMR, FTIR, UV-visible and ESI-MS techniques. DNA interaction of isolated compounds with calf thymus (CT-DNA) was explored by UV-vis absorption, fluorescence, cyclic voltametric and viscometric methods. The result shows that prepared compounds can interact with CT-DNA through electrostatic interactions. Bovine serum album (BSA) binding behavior of isolated compounds was also studied by UV-vis absorption and fluorescence techniques. Both the spectroscopic results suggest that the isolated ligand and its complex bind with BSA through static quenching. The optimized structure of ligand and platinum complex were achieved by the DFT calculations. Moreover, molecular docking of ligand and its complex were studied. These analysis results reveal that ligand has low binding affinity on DNA and BSA molecules in contrast to its complex. In vitro anticancer activity of isolated compounds toward normal cell line (NHDF) as well as cancer cell lines (MCF-7, HepG2, HeLa and A549) was studied by MTT assay. The results supports that isolated platinum complex can control the growth of cancer cells (MCF-7, 20.12 ± 1.00 µg/mL; HepG2, 32.2 ± 1.69 µg/mL; HeLa, 24.68 ± 1.29 µg/mL; A549, 23.46 ± 1.17 µg/mL) without inhibiting the normal cell line (NHDF, 109.26 ± 5.46 µg/mL). Antioxidant and antimicrobial activities of isolated compounds indicate that ligand and Pt complex are found to have good radical scavenging against four different free radicals and antimicrobial abilities on E. coli and C. albicans antimicrobial species. HighlightsPlatinum complex of Schiff base with pyrimidine and morpholine linkage was synthesized.Pt complex has better biomolecular interaction with DNA and BSA.Molecular docking of Pt complex with DNA and BSA has been studiedPt complex has good anticancer activities.Pt complex has better antioxidant and antimicrobial activities.

Water soluble Cu(II) and Zn(II) complexes of bidentate-morpholine based ligand: synthesis, spectral, DFT calculation, biological activities and molecular docking studies.

Copper(II) and zinc(II) complexes of the type [ML(AcO)2.H2O] were synthesized from bidentate-morpholine based Schiff base ligand (L - morpholinopropylimino)methyl)-6-methoxyphenol). The prepared ligand, copper(II) and zinc(II) complexes were characterized by elemental analysis, ESI-MS, 1H-NMR, FT-IR, UV-Visible, ESR and spectrometric methods. The elemental and ESI-MS results have been established that the prepared ligand and complexes possess 1:1 stoichiometric ratio. 1H-NMR and FT-IR results have been suggested that azomethine nitrogen and morpholine ring nitrogen atoms are coordinated with Cu(II) and Zn(II) metal ions. UV-Visible, ESI-MS and ESR spectroscopic results have been supported that the proposed structure of Cu(II) and Zn(II) complexes possess square pyramidal geometry. In order to confirm the proposed square pyramidal geometry of prepared complexes by DFT calculation has been studied. DNA binding ability of Cu(II) and Zn(II) complexes have been studied by electronic absorption and viscometric methods. These results reveal that Cu(II) and Zn(II) complexes interact with CT-DNA by the way of groove binding mode. Molecular docking studies result shows that synthesized compounds has better binding ability. The in vitro antioxidant activities of ligand, Cu(II) and Zn(II) complexes have been investigated by using the DPPH assay. The result shows that synthesized compounds have good radical scavenging activity against DPPH radical. Antimicrobial activities of synthesized ligand and its complexes have been tested against selected bacterial (gram positive & gram negative) and fungal species. The results reveal that Cu(II) and Zn(II) have good antimicrobial activity than ligand.Communicated by Ramaswamy H. Sarma.

An open clinical evaluation of selected siddha regimen in expediting the management of COVID-19 -a randomized controlled study.

BACKGROUND: The corona virus disease 2019 (COVID-19), an acute respiratory disease, caused by a novel corona virus (SARS-CoV-2, previously known as 2019-nCoV), obtained worldwide attention. In this review, we explored the potential siddha strategies for COVID -19 infections. OBJECTIVES: To evaluate the additional benefits of siddha drugs Vasantha kusumakaram mathirai, Thippili rasayanam, Adathodai manapagu and Kabasura kudineer compared to the allopathic standard treatment of care alone in COVID-19 asymptomatic, mild - moderate cases. MATERIALS AND METHODS: The present study was an open label Two arm - randomized controlled interventional clinical study. The Group I patients were assigned to Siddha add on treatment whereas Group II subjects were assigned with standard treatment alone. The sample size was 100 for each group. RESULT: The average number of days taken for reduction of symptoms showed significant results (P < 0.001) in Siddha add on compared with standard treatment. The real - time polymerase chain reaction (RT-PCR) investigation turned negative for 78.33% in Siddha add on and 33.33% in standard treatment after 11-14 days. Similarly, CT chest, covid pattern lung involvement percentage showed highly significant reduction (P < 0.0001) in Siddha add on treatment. In addition, Neutrophil Lymphocyte Ratio (NLR) ratio, showed significant reduction (P < 0.01) when analyzed by Wilcoxon signed rank test, and Renal, Liver parameters were within the normal limits in Siddha add on Group for 25 samples in post treatment. CONCLUSION: Finally, it was concluded that Siddha add on Group showed accelerated recovery for COVID - 19 patients compared to standard Group. The synergistic effect of Siddha add on with standard treatment gave more promising results in the current study of COVID -19.

G4 Sensing Pyridyl-Thiazole Polyamide Represses c-KIT Expression in Leukemia Cells.

Specific sensing and functional tuning of nucleic acid secondary structures remain less explored to date. Herein, we report a thiazole polyamide TPW that binds specifically to c-KIT1 G-quadruplex (G4) with sub-micromolar affinity and ∼1 : 1 stoichiometry and represses c-KIT proto-oncogene expression. TPW shows up to 10-fold increase in fluorescence upon binding with c-KIT1 G4, but shows weak or no quantifiable binding to other G4s and ds26 DNA. TPW can increase the number of G4-specific antibody (BG4) foci and mark G4 structures in cancer cells. Cell-based assays reveal that TPW can efficiently repress c-KIT expression in leukemia cells via a G4-dependent process. Thus, the polyamide can serve as a promising probe for G-quadruplex recognition with the ability to specifically alter c-KIT oncogene expression.

Emerging Therapeutic Approaches to Combat COVID-19: Present Status and Future Perspectives.

Coronavirus disease (COVID-19) has emerged as a fast-paced epidemic in late 2019 which is disrupting life-saving immunization services. SARS-CoV-2 is a highly transmissible virus and an infectious disease that has caused fear among people across the world. The worldwide emergence and rapid expansion of SARS-CoV-2 emphasizes the need for exploring innovative therapeutic approaches to combat SARS-CoV-2. The efficacy of some antiviral drugs such as remdesivir, favipiravir, umifenovir, etc., are still tested against SARS-CoV-2. Additionally, there is a large global effort to develop vaccines for the protection against COVID-19. Because vaccines seem the best solution to control the pandemic but time is required for its development, pre-clinical/clinical trials, approval from FDA and scale-up. The nano-based approach is another promising approach to combat COVID-19 owing to unique physicochemical properties of nanomaterials. Peptide based vaccines emerged as promising vaccine candidates for SARS-CoV-2. The study emphasizes the current therapeutic approaches against SARS-CoV-2 and some of the potential candidates for SARS-CoV-2 treatment which are still under clinical studies for their effectiveness against SARS-CoV-2. Overall, it is of high importance to mention that clinical trials are necessary for confirming promising drug candidates and effective vaccines and the safety profile of the new components must be evaluated before translation of in vitro studies for implementation in clinical use.

A DNA nanosensor for monitoring ligand-induced i-motif formation.

Herein, we present a gold nanoparticle (GNP)-based DNA nanosensor to detect the formation of an i-motif from the random coil structure by small molecules at physiological pH. The nanosensor shows a distance dependent fluorescence turn-off response in the presence of a ligand, indicating conformational changes from the C-rich single stranded DNA into an i-motif.

Carbon Dot Cross-Linked Gelatin Nanocomposite Hydrogel for pH-Sensing and pH-Responsive Drug Delivery.

Delivery of therapeutics to the intestinal region bypassing the harsh acidic environment of the stomach has long been a research focus. On the other hand, monitoring a system's pH during drug delivery is a crucial diagnosis factor as the activity and release rate of many therapeutics depend on it. This study answered both of these issues by fabricating a novel nanocomposite hydrogel for intestinal drug delivery and near-neutral pH sensing at the same time. Gelatin nanocomposites (GNCs) with varying concentrations of carbon dots (CDs) were fabricated through simple solvent casting methods. Here, CDs served a dual role and simultaneously acted as a cross-linker and chromophore, which reduced the usage of toxic cross-linkers. The proposed GNC hydrogel sample acted as an excellent pH sensor in the near-neutral pH range and could be useful for quantitative pH measurement. A model antibacterial drug (cefadroxil) was used for the in vitro drug release study at gastric pH (1.2) and intestinal pH (7.4) conditions. A moderate and sustained drug release profile was noticed at pH 7.4 in comparison to the acidic medium over a 24 h study. The drug release profile revealed that the pH of the release medium and the percentage of CDs cross-linking influenced the drug release rate. Release data were compared with different empirical equations for the evaluation of drug release kinetics and found good agreement with the Higuchi model. The antibacterial activity of cefadroxil was assessed by the broth microdilution method and found to be retained and not hindered by the drug entrapment procedure. The cell viability assay showed that all of the hydrogel samples, including the drug-loaded GNC hydrogel, offered acceptable cytocompatibility and nontoxicity. All of these observations illustrated that GNC hydrogel could act as an ideal pH-monitoring and oral drug delivery system in near-neutral pH at the same time.

Recurrent refractive error after myopic laser-assisted in situ keratomileusis - What could be the reason?

Recurrence of myopia after myopic LASIK reduces the outcome of the procedure. Important causes include post-LASIK ectasia, regression of myopia, accommodative strain, and lens or axial length changes. Herein, we present a case of myopia recurring after LASIK and try to arrive at the possible diagnosis among these, as the treatment differs for each. The detailed evaluation showed that our patient had regression of myopia after LASIK. Of the multiple causes for recurrence of refractive error after myopic laser vision correction, it is important to identify the relevant reason as the treatment and prognosis for each of these is different.

Biosilica slab photonic crystals as an alternative to cleanroom nanofabrication?

Photonics, the manipulation of light at nanoscale, is a key enabling technology with impact in health and energy applications, among others. In most cases photonics still relies on materials and fabrication methods inherited from other disciplines, usually requiring expensive, time-consuming and environmentally-unfriendly processes. Recent experiments demonstrated that advanced photonic materials, as complex as those known as 2.5 dimensional slab photonic crystals, also occur naturally in diatoms. These microscopic algae precipitate silicic acid from water to produce silicon dioxide membranes, relying on intracellular biomineralization mechanisms. Addressing some important aspects for the potential industrial utilization of these structures, we here propose that optical materials produced by the diatoms could serve as cost-effective and environmentally friendly alternatives to cleanroom nanofabrication. We demonstrate that photonic materials grown by the diatom species Coscinodiscus granii can be separated based on its hydrokinetic characteristics. We further show that the photonic membranes present low defect rates of ca. 1/100 unit cells and that variation in pore diameter, as observed between individual membranes, can affect the photonic properties at large, but only marginally at low refractive index contrast. Finally, we list algal culture collections operating worldwide, thus providing a global network for live diatoms and diatom materials. We discuss the feasibility and bottlenecks related to scaled-up growth for direct utilization of photonic materials from diatoms.