Screening Carbon Nano Materials for Preventing Amyloid Protein Aggregation by Adopting a Facile Method.

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others are associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates, including oligomers, continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively and quantitatively report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive, and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

Screening Carbon Nano Materials for preventing amyloid protein aggregation by adopting a facile method.

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others is associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. The dissolution of mature fibrils and toxic amyloidogenic intermediates including oligomers continues to be the pinnacle in the treatment of neurodegenerative disorders. Yet, methods to effectively, and quantitatively, report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. Here we describe a simplified method that implements the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique implements an optimized but well-known, simple, inexpensive and quantitative assessment previously used to assess the oligomerization of amyloid monomers and subsequent amyloid fibrils. This method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers, dimers, and trimers and/or retain amyloid proteins in their monomeric forms. Most importantly, our optimized method diminishes existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

Randomized Controlled Trial of Isha Kriya versus Observation to Improve Quality of Life in Hematopoietic Cell Transplantation Recipients.

Hematopoietic cell transplantation (HCT) impacts recipients' quality of life (QoL). Few mindfulness-based interventions (MBI) in HCT recipients have shown feasibility, but heterogeneous practices and outcome measures have called into question the actual benefit. We hypothesized that self-guided isha kriya, a 12-minute guided meditation based on the principles of yoga focusing on breathing, awareness, and thought, as a mobile app would improve QoL in the acute HCT setting. This single-center, open-label, randomized controlled trial was conducted in 2021 to 2022. Autologous and allogeneic HCT recipients age ≥18 years were included. The study was approved by our Institutional Ethics Committee and registered at the Clinical Trial Registry of India, and all participants provided written informed consent. HCT recipients without access to smartphones or regular practitioners of yoga, meditation, or other mind-body practices were excluded. Participants were randomized to the control arm or the isha kriya arm at a 1:1 ratio stratified by type of transplantation. Patients in the isha kriya arm were instructed to perform the kriya twice daily from pre-HCT to day +30 post-HCT. The primary endpoint was QoL summary scores as assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) and the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS-GH) questionnaires. The secondary endpoints were the differences in QoL domain scores. The validated questionnaires were self-administered before the intervention and at days +30 and +100 post-HCT. The analysis of endpoints was done on an intention-to-treat basis. Domain and summary scores were calculated for each instrument as recommended by the developers. A P value < .05 was considered to indicate statistical significance, and Cohen's d effect size was used to determine clinical significance. A total of 72 HCT recipients were randomized to the isha kriya and control arms. Patients in the 2 arms were matched for age, sex, diagnosis, and type of HCT. The 2 arms showed no differences in pre-HCT QoL domain, summary, and global scores. At day +30 post-HCT, there was no difference between the arms in the mean FACT-BMT total score (112.9 ± 16.8 for the isha kriya arm versus 101.2 ± 13.9 for the control arm; P = .2) or the mean global health score (global mental health, 45.1 ± 8.6 versus 42.5 ± 7.2 [P = .5]; global physical health, 44.1 ± 6.3 versus 44.1 ± 8.3 [P = .4]) in the 2 groups. Similarly, there were no differences in physical, social, emotional, and functional domain scores. However, the mean bone marrow transplantation (BMT) subscale scores, which addresses BMT-specific QoL concerns, were statistically and clinically significantly higher in the isha kriya arm (27.9 ± 5.1 versus 24.4 ± 9.2; P = .03; Cohen's d = .5; medium effect size). This effect was transient; mean day +100 scores showed no difference (28.3 ± 5.9 versus 26.2 ± 9.4; P = .3). Our data indicate that the isha kriya intervention did not improve the FACT-BMT total and global health scores in the acute HCT setting. However, practicing isha kriya for 1 month was associated with transient improvement in the FACT-BMT subscale scores on day +30 but not on day +100 post-HCT.

Resolving the soluble-to-toxic transformation of amyloidogenic proteins: A method to assess intervention by small-molecules.

The soluble-to-toxic transformation of intrinsically disordered amyloidogenic proteins such as amyloid beta (Aß), α-synuclein, mutant Huntingtin Protein (mHTT) and islet amyloid polypeptide (IAPP) among others is associated with disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Type 2 Diabetes (T2D), respectively. Conversely, the dissolution of mature fibrils and toxic amyloidogenic intermediates including oligomers remains the holy grail in the treatment of neurodegenerative disorders. Yet, methods to effectively, and quantitatively, report on the interconversion between amyloid monomers, oligomers and mature fibrils fall short. For the first time, we describe the use of gel electrophoresis to address the transformation between soluble monomeric amyloid proteins and mature amyloid fibrils. The technique permits rapid, inexpensive and quantitative assessment of the fraction of amyloid monomers that form intermediates and mature fibrils. In addition, the method facilitates the screening of small molecules that disintegrate oligomers and fibrils into monomers or retain amyloid proteins in their monomeric forms. Importantly, our methodological advance diminishes major existing barriers associated with existing (alternative) techniques to evaluate fibril formation and intervention.

Gelatin-derived carbon quantum dots mitigate herbicide-induced neurotoxic effects in vitro and in vivo.

The herbicide and viologen, N, N'-dimethyl-4,4'-bipyridinium dichloride (Paraquat) is known to be toxic to neuronal cells by a multifactorial process involving an elevation in the levels of reactive oxygen species (ROS), the triggering of amyloid-protein aggregation and their accumulation, collectively leading to neuronal dyshomeostasis. We demonstrate that green-chemistry-synthesized sustainable gelatin-derived carbon quantum dots (CQDs) mitigate paraquat-induced neurotoxic outcomes and resultant compromise in organismal mortality. Gelatin-derived CQDs were found to possess antioxidant properties and ameliorated ROS elevation in paraquat-insulted neuroblastoma-derived SHSY-5Y cells, protecting them from herbicide-induced cell death. These CQDs also increased lifespan in paraquat-compromised Caenorhabditis elegans and herbicide-mediated dopamine neuron ablation. Collectively, the data underscore the ability of this sustainably synthesized, environmentally friendly biocompatible nanomaterial to protect cell lines and organisms against neurotoxic outcomes. The study findings strategically position this relatively novel nanoscopic carbon quantum framework for further testing in vertebrate trials of neurotoxic insult.

Citric Acid-Derived Carbon Quantum Dots Attenuate Paraquat-Induced Neuronal Compromise In Vitro and In Vivo.

The potent environmental herbicide and weedicide paraquat is linked to neuromotor defects and Parkinson's disease (PD). We have evaluated the neuroprotective role of citric acid-sourced carbon quantum dots (Cit-CQDs) on paraquat-insulted human neuroblastoma-derived SH-SY5Y cell lines and on a paraquat-exposed nematode (Caenorhabditis elegans). Our data reveal that Cit-CQDs are able to scavenge free radicals in test tube assays and mitigate paraquat-elevated reactive oxygen species (ROS) levels in SH-SY5Y cells. Furthermore, Cit-CQDs protect the cell line from paraquat, which otherwise elicits cell death. Cit-CQDs-challenged nematodes demonstrate enhanced survival rates 72 h post-paraquat exposure compared to controls. Paraquat ablates dopamine (DA) neurons, which results in compromised locomotor function in nematodes. However, the neurons remained intact when the nematodes were incubated with Cit-CQDs prior to neurotoxicant exposure. The collective data suggest Cit-CQDs offer neuroprotection for cell lines and organisms from xenotoxicant-associated neuronal injury and death. The study suggests Cit-CQDs as a potentially viable green chemistry-synthesized, biobased nanomaterial for intervention in neurodegenerative disorders.

The Effect of Ascophyllum nodosum Extract on the Nutraceutical Antioxidant Potential of Vigna radiata Sprout under Salt Stress.

Mung bean (Vigna radiata L.) sprout is a popular fresh vegetable, tasty and high in antioxidants. To increase yield and quality after the occurrence of both abiotic and biotic stresses, the application of seaweed extracts is of great importance. Hence, this study was conducted to determine the effect of Ascophyllum nodosum extract (ANE) in the presence of salt on the antioxidant potential of V. radiata sprouts. Different concentrations of ANE viz. 0.00, 0.01, 0.05, 0.10, and 0.50% and NaCl 0, 25, 50, 75, and 100 mM alone and in combinations were tested for researching the antioxidant potential of V. radiata sprouts at 0, 24, and 36 h of sprouting. The DPPH free-radical-scavenging activity of sprouts of V. radiata was found to increase with time and peaked at 24 h of treatment. The A. nodosum extract (0.01%) could reverse the ill effect of the low level of salinity posed by up to 25 mM NaCl. The increasing salinity deteriorated the antioxidant activity using ABTS method of sprouts down to 20.45% of the control at 100 mM NaCl. The total phenolic content (TPC), total flavonoid content (TFC), and reducing power of V. radiata sprouts was found to increase till 36 h of sprouting. A slight increase in TPC, TFC and reducing power was observed when seeds were treated with low concentrations of ANE. The elevation in TPC, TFC and reducing power upon treatment with low concentrations of ANE was also noticed in sprouts in saline combinations. Alpha amylase inhibition activity was found to reach a (67.16% ± 0.9) maximum at 24 h of sprouting at a 0.01% concentration of ANE. Tyrosinase inhibition and alpha glucosidase inhibition was 88.0% ± 2.11 and 84.92% ± 1.2 at 36 h of sprouting, respectively, at 0.01% concentration of ANE. A. nodosum extract is natural, environmentally friendly, and safe, and could be used as one of the strategies to decline stress at a low level and enhance the antioxidant activities in V. radiata sprouts, thus increasing its potential to be developed as an antioxidant-based functional food.

Carbon Quantum Dots for Treatment of Amyloid Disorders.

Prion-like amyloids self-template and form toxic oligomers, protofibrils, and fibrils from their soluble monomers; a phenomenon that has been implicated in the onset and progress of neurodegenerative disorders such as Alzheimer's (AD), Parkinson's (PD), Huntington's, and systemic lysozyme amyloidosis. Carbon quantum dots (CQDs), sourced from Na-citrate as a carbon precursor were synthesized and characterized before being tested for their ability to intervene in amyloidogenic (fibril-forming) trajectories. Hen-egg white lysozyme (HEWL) served as a model amyloidogenic protein. A pulse-chase lysozyme fibril-forming assay developed to examine the impact of CQDs on the HEWL amyloid-fibril-forming trajectory used ThT fluorescence as a reporter of mature fibril presence. The results revealed that the Na-citrate-derived CQDs were able to intervene at multiple points along the fibril-forming trajectory by preventing the conversion of both monomeric and oligomeric HEWL intermediates into mature fibrils. In addition, and importantly, the carbon nano material (CNM) was able to dissolve oligomeric HEWL into monomeric HEWL and provoke the disaggregation of mature HEWL fibrils. These results suggest that Na-citrate CQD's intervene in amyloidogenesis by multiple mechanisms. The gathered data, coupled with cell-line results demonstrating the relatively low cytotoxicity of Na-citrate CQDs, suggest that this emerging CNM has the potential to intervene both prophylactically and therapeutically in protein misfolding diseases. The aforementioned findings are likely to enable Na-citrate CQDs to eventually transition to both cell-line and preclinical models of protein-misfolding-related disorders. Importantly, the study outcomes positions Na-citrate CQDs as an important class of chemical, nanotechnological, and biobased interventional tools in neuroscience.

Chitosan-Ellagic Acid Nanohybrid for Mitigating Rotenone-induced Oxidative Stress.

Antioxidants derived from nature, such as ellagic acid (EA), demonstrated high potency to mitigate neuronal oxidative stress and related pathologies, including Parkinson's disease. However, the application of EA is limited due to its toxicity at moderate doses and poor solubility, cellular permeability, and bioavailability. Here, we introduce a sustainably resourced, green nanoencasement strategy to overcome the limitations of EA and derive synergistic effects to prevent oxidative stress in neuronal cells. Chitosan, with its high biocompatibility, potential antioxidant properties, and flexible surface chemistry, was chosen as the primary component of the nanoencasement in which EA is immobilized. Using a rotenone model to mimic intracellular oxidative stress, we examined the effectiveness of EA and chitosan to limit cell death. Our studies indicate a synergistic effect between EA and chitosan in mitigating rotenone-induced reactive oxygen species death. Our analysis suggests that chitosan encapsulation of EA reduces the inherent cytotoxicity of the polyphenol (a known anticancer molecule). Furthermore, its encapsulation permits its delivery via a rapid burst phase and a relatively slow phase making the nanohybrid suitable for drug release over extended time periods.

Chitosan Nanoparticles Rescue Rotenone-Mediated Cell Death.

The aim of the present investigation was to study the anti-oxidant effect of chitosan nanoparticles on a human SH-SY5Y neuroblastoma cell line using a rotenone model to generate reactive oxygen species. Chitosan nanoparticles were synthesized using an ionotropic gelation method. The obtained nanoparticles were characterized using various analytical techniques such as Dynamic Light Scattering, Scanning Electron Microscopy, Transmission Electron Microscopy, Fourier Transmission Infrared spectroscopy and Atomic Force Microscopy. Incubation of SH-SY5Y cells with 50 µM rotenone resulted in 35-50% cell death within 24 h of incubation time. Annexin V/Propidium iodide dual staining verified that the majority of neuronal cell death occurred via the apoptotic pathway. The incubation of cells with chitosan nanoparticles reduced rotenone-initiated cytotoxicity and apoptotic cell death. Given that rotenone insult to cells causes oxidative stress, our results suggest that Chitosan nanoparticles have antioxidant and anti-apoptotic properties. Chitosan can not only serve as a novel therapeutic drug in the near future but also as a carrier for combo-therapy.

Enhancing the Delivery of Chemotherapeutics: Role of Biodegradable Polymeric Nanoparticles.

While pharmaceutical drugs have revolutionized human life, there are several features that limit their full potential. This review draws attention to some of the obstacles currently facing the use of chemotherapeutic drugs including low solubility, poor bioavailability and high drug dose. Overcoming these issues will further enhance the applicability and potential of current drugs. An emerging technology that is geared towards improving overall therapeutic efficiency resides in drug delivery systems including the use of polymeric nanoparticles which have found widespread use in cancer therapeutics. These polymeric nanoparticles can provide targeted drug delivery, increase the circulation time in the body, reduce the therapeutic indices with minimal side-effects, and accumulate in cells without activating the mononuclear phagocyte system (MPS). Given the inroads made in the field of nanodelivery systems for pharmaceutical applications, it is of interest to review and emphasize the importance of Polymeric nanocarrier system for drug delivery in chemotherapy.

Newer proposed classification of periimplant defects: A critical update.

The term peri-implantitis is used to describe a destructive inflammatory process affecting the soft and hard tissues around osseo integrated implants, leads to the formation of a peri-implant pocket and loss of supporting bone. Predisposing factors are Poor Plaque Control, inflammation, infection, Smoking, Diabetes and Occlusal Overload. It is diagnosed on the basis of clinical and radiographic interpretation and still no definite criteria have been proposed for the diagnosis and treatment of peri-implantitis. However treatment can be both conservative and surgical. The cumulative interceptive supportive therapy protocol serves as good guide for the treatment of the peri-implantitis. There is lack of a standard classification system to differentiate the various degrees of peri-implantitis, which produces dilemma in evaluating the stages clinical and radiological status, treatment and its outcome. Many classification has been proposed in medical literature with their pros and cons but still there is lack of standard classification system of implant defects and definite treatment protocol according to the same. The classification should be easy to use, clearly understandable and help in communication by clinicians of different speciality. This review aimed to introduce a classification system based on added clinical, and detailed radiological parameters with prognosis and staged treatment algorithms.

Treatment modalities for surgical management of anterior palatal fistula: Comparison of various techniques, their outcomes, and the factors governing treatment plan: A retrospective study.

AIM: Aim of this retrospective study was to access the various surgical treatment options available for repair of Anterior palatal fistula depending upon their size and presenting age, and also to anticipate the treatment outcome. MATERIALS AND METHODS: The series include study report of forty patients with secondary anterior palatal fistula post cleft palate repair, reported in a single unit during a duration of 3 years. All the cases were managed surgically under general anesthesia. The patients were classified depending upon the location of anterior palatal fistula (APF), the quality of tissue and age of patients to chalk out a justified treatment option outlay. RESULTS: Forty cases were split for surgical correction into various options depending on their size, site, and quality of the tissue. Most of the cases were operated with a Bardach's Redo for fistula closure (n = 16) (40%) and crevicular flap technique (n = 13) (32.5%). Our overall success (satisfactory results) was 77.5% as observed in 31 out of 40 cases with individual success rates for Bardach's and crevicular being 75% and 77%, respectively. There was reduction in size of fistula in three cases (7.5%) and a remnant pinpoint hole in four cases (10%) among all the operated cases. CONCLUSION: Management of post palatoplasty fistulas of the hard palate presents a challenging situation for a clinician following the surgical correction of cleft palate. Current paper describes the diagnosis and clinical management of forty cases reporting with unilateral APF following cleft palate surgery, over 3 years. Authors have attempted to propose different treatment modalities for surgical management of unilateral APF. It was concluded in the primary review that the size of fistula was irrelevant in determining the clinical outcome. Instead, the quality and condition of the adjacent tissue appear to be the major governing factors for selecting treatment modality as well as the surgical consequences.