Phytomolecules from conventional to nano form: Next-generation approach for Parkinson's disease.

The incidence of neurodegenerative diseases is increasing exponentially worldwide. Parkinson's disease (PD) is a neurodegenerative disease caused by factors like oxidative stress, gene mutation, mitochondrial dysfunction, neurotoxins, activation of microglial inflammatory mediators, deposition of Lewy's bodies, and α- synuclein proteins in the neurons leading to neuroinflammation and neurodegeneration in the substantia nigra. Hence the development of efficacious neuro-therapy is in demand which can prevent neurodegeneration and protect the nigrostriatal pathway. One of the approaches for managing PD is reducing oxidative stress due to aging and other co-morbid diseased conditions. The phytomolecules are reported as safe and efficacious antioxidants as they contain different secondary metabolites. However, the limitations of low solubility restricted permeability through the blood-brain barrier, and low bioavailability limits their clinical evaluation and application. This review discusses the therapeutic efficacy of phytomolecules in PD and different nanotechnological approaches to improve their brain permeability.

Comparison of crestal bone loss and papilla fill after conventional and immediate implant placement: A 12 month clinical and radiographic prospective study.

Background: The problem of missing teeth persists in all age groups. The main objective of implants in dentistry is to provide a restoration that reconstructs the shape and restores esthetics and functions of edentulous areas. The objectives of this study are to compare the crestal bone level changes and papillary fill after placement of implants in fresh extraction socket, i.e. immediate implant placement, and healed extraction socket, i.e. delayed or conventional implant placement, and to assess other clinical parameters such as modified plaque index (mPI), modified gingival index (mGI) and gingival biotype in between the groups and within the groups. Methods: 18 patients were recruited in the study out of which 9 patients received implants as per immediate implant placement protocol (group 1) and 9 patients received implants as per conventional implant placement protocol (group 2). All patients were evaluated for gingival biotype, mPI and mGI and papillary fill was assessed as per Jemt's papilla score as clinical parameters. Implant site was assessed for radiographic bone loss using Image J software. Statistical analysis was performed using independent t test, paired t test and chi square test. Results: At the end of 1 year, results showed that crestal bone loss was seen more in the immediate group than the conventional group. Conventional implants showed better papillary fill than implants placed in fresh extraction sockets. Plaque scores were assessed as per modified plaque index, which showed better results in the conventional group. Modified gingival index was used to assess gingival status which showed better results in the immediate group one year later. Conclusions: Findings from the study suggest that crestal bone loss was found to be increased in the immediate group than the conventional group and papillary fill was better in the conventional group than the immediate group.Registration: CTRI ( CTRI/2019/09/021340).

Metal Nanoparticles in Alzheimer's Disease.

Nanotechnology has emerged in different fields of biomedical application, including lifestyle diseases like diabetes, hypertension, and chronic kidney disease, neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease, and different types of cancers. Metal nanoparticles are one of the most used drug delivery systems due to the benefits of their enhanced physicochemical properties as compared to bulk metals. Neurodegenerative diseases are the second most cause affecting mortality worldwide after cancer. Hence, they require the most specific and targeted drug delivery systems for maximum therapeutic benefits. Metal nanoparticles are the preferred drug delivery system, possessing greater blood-brain barrier permeability, biocompatibility, and enhanced bioavailability. But some metal nanoparticles exhibit neurotoxic activity owing to their shape, size, surface charge, or surface modification. This review article has discussed the pathophysiology of AD. The neuroprotective mechanism of gold, silver, selenium, ruthenium, cerium oxide, zinc oxide, and iron oxide nanoparticles are discussed. Again, the neurotoxic mechanisms of gold, iron oxide, titanium dioxide, and cobalt oxide are also included. The neuroprotective and neurotoxic effects of nanoparticles targeted for treating AD are discussed elaborately. The review also focusses on the biocompatibility of metal nanoparticles for targeting the brain in treating AD. The clinical trials and the requirement to develop new drug delivery systems are critically analyzed. This review can show a path for the researchers involved in the brain-targeted drug delivery for AD.

Ameliorative and Neuroprotective Effect of Core-Shell Type Se@Au Conjugated Hesperidin Nanoparticles in Diabetes-Induced Cognitive Impairment.

Diabetes mellitus is the most chronic metabolic ailment characterized by insulin deficiency leading to aberrant cognitive dysfunction in later stages. Hesperidin is a bioflavonoid, having different pharmacological activities, but its poor water solubility and short plasma half-life restrict its applications in the clinical field. So, the hesperidin was conjugated with gold, selenium, and core-shell bimetallic nanoparticles of gold and selenium. Different spectroscopic methods characterized the synthesized monometallic and bimetallic nanoparticles. The rats were injected with streptozotocin to induce cognitive dysfunction, followed by administering HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs daily for 21 days. Then, the neurobehavioral studies, oxidative stress parameters, AChE and nitrite levels, the content of amyloid-ß42, and inflammatory mediators were accessed to evaluate the effect of the nanoparticles against the STZ rat model. The results showed a significant increase in oxidative stress, AChE activity, amyloid-ß42, nitrite levels, and neuroinflammation by upregulating the inflammatory cytokines in the streptozotocin-administered rat brain. The HSP, HSP-Au NPs, HSP-Se NPs, and Se@Au-HSP NPs effectively reversed all these effects of streptozotocin. However, the bimetallic nanoparticle Se@Au-HSP NPs revealed better neuroprotective action than HSP-Au NPs and HSP-Se NPs. Hesperidin-conjugated bimetallic nanoparticles improved learning and memory in the STZ rat model and may be an alternative approach for neurodegenerative diseases, including Alzheimer's disease.

New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder affecting a major class of silver citizens. The disorder shares a mutual relationship on account of its cellular and molecular pathophysiology with type-II diabetes mellitus (DM). Chronic DM increases the risk for AD. Emerging evidence recommended that resistance in insulin production develops cognitive dysfunction, which generally leads to AD. Repurposing of antidiabetic drugs can be effective in preventing and treatment of the neurodegenerative disorder. Limitations of antidiabetic drugs restrict the repurposing of the drugs for other disorders. Therefore, nanotechnological intervention plays a significant role in the treatment of neurological disorders. In this review, we discuss the common cellular and molecular pathophysiologies between AD and type-II DM, the relevance of in vivo models of type II DM in the study of AD, and the repurposing of antidiabetic drugs and the nanodelivery systems of antidiabetic drugs against AD.

Interplay of lipid head group and packing defects in driving amyloid-beta-mediated myelin-like model membrane deformation.

Accumulating evidence suggests that amyloid plaque-associated myelin lipid loss as a result of elevated amyloid burden might also contribute to Alzheimer's disease. The amyloid fibrils are closely associated with lipids under physiological conditions; however, the progression of membrane remodeling events leading to lipid-fibril assembly remains unknown. Here we first reconstitute the interaction of amyloid Beta 40 (Aß-40) with myelin-like model membrane and show that the binding of Aß-40 induces extensive tubulation. To look into the mechanism of membrane tubulation, we chose a set of membrane conditions varying in lipid packing density and net charge that allows us to dissect the contribution of lipid specificity of Aß-40 binding, aggregation kinetics, and subsequent changes in membrane parameters such as fluidity, diffusion, and compressibility modulus. We show that the binding of Aß-40 depends predominantly on the lipid packing defect densities and electrostatic interactions and results in rigidification of the myelin-like model membrane during the early phase of amyloid aggregation. Furthermore, elongation of Aß-40 into higher oligomeric and fibrillar species leads to eventual fluidization of the model membrane followed by extensive lipid membrane tubulation observed in the late phase. Taken together, our results capture mechanistic insights into snapshots of temporal dynamics of Aß-40-myelin-like model membrane interaction and demonstrate how short timescale, local phenomena of binding, and fibril-mediated load generation results in the consequent association of lipids with growing amyloid fibrils.

GB1 Dimerization in Crowders: A Multiple Resolution Approach.

In-cell protein-protein association, which is crucial in enzyme catalysis and polymerization, occurs in an environment that is highly heterogeneous and crowded. The crowder molecules exclude the reactant molecules from occupying certain regions of the cell, resulting in changes in the reaction thermodynamics and kinetics. Recent studies, both experiment and simulations, revealed that the nature of the interaction between crowder and protein species, in particular the soft interactions, plays an important role in crowder induced effects on protein association. To this end, from a simulation perspective, it is important to decipher the level of structural resolution in a protein-crowder model that can faithfully capture the influence of crowding on protein association. Here, we investigate the dimerization of model system GB1 in the presence of lysozyme crowders at two structural resolutions. The lower resolution model assumes both protein and crowder species as spherical beads, similar to the analytical scaled particle theory model, whereas the higher resolution model retains residue specific structural details for protein and crowder species. From the higher resolution model, it is found that GB1 dimer formation is destabilized in the presence of lysozyme crowders, and the destabilization is more for the side-by-side dimer compared to the domain-swapped dimer, in qualitative agreement with experimental findings. However, the low resolution CG model predicts stabilization of the dimers in the presence of the lysozyme crowder, similar to the SPT model. Our results indicate a nontrivial role of the choice of model resolution in computer simulation studies investigating crowder induced effects.

Photocatalysis of environmental organic pollutants and antioxidant activity of flavonoid conjugated gold nanoparticles.

The unique properties of nanomaterials have the potential application in different fields of biomedical application along with the management of environmental pollutants. This research work involved the isolation of hesperidin from the orange peel and the preparation of hesperidin gold nanoparticles by the chemical reduction method. The high substrate specificity and lower band gap enable the excitation of gold nanoparticles in visible light. Hence gold nanoparticles are chosen nowadays for the management and removal of organic pollutants. The efficacy of hesperidin gold nanoparticles was evaluated by the photocatalytic activity on organic dyes and pollutants like methyl orange, methylene blue, bromocresol green, and 4 - nitro phenol with sodium borohydride as reducing agent and the antioxidant study by scavenging of free radicals of DPPH, ABTS, and hydroxyl free radicals of hydrogen peroxide. The kinetics of photocatalytic degradation of organic dyes and 4 - nitro phenol was found to follow the first order with rate constants of 10 × 10-3, 37 × 10-3, 23 × 10-3 and 49 × 10-3 min-1 for methyl orange, methylene blue, bromocresol green and 4 - nitro phenol respectively. The hesperidin gold nanoparticles showed significant antioxidant activity as compared to ascorbic acid as standard. The flavonoid conjugated gold nanoparticles can be an efficient antioxidant and photocatalyst for the management of different diseases and wastewater treatment respectively.

Title-comparison of coronally advanced flap with chorion membrane vs coronally advanced flap with connective tissue graft in the treatment of multiple gingival recessions: a split-mouth randomised controlled study.

Background: The importance of esthetics has escalated over the years. The purpose of any perioplastic surgery is to address gingival recession while ensuring predictable root coverage and a pleasing appearance. An array of surgical procedures have been recommended for the management of recession defects. The present study compares the clinical and patient related outcome measures of coronally advanced flap with chorion membrane and connective tissue graft in the management of multiple adjacent gingival recessions. Methods: The study was a prospective randomized controlled trial which included eight systemically healthy patients with an age range of 30-44 years with 36 labial/buccal, multiple adjacent, Cairo's RT1 gingival recession defects, bilaterally.  CAF+CM was performed on one side whereas CAF+CTG was performed on the other side. The two groups were compared clinically at three and six months postoperatively. Results: There was statistically significant decrease in recession depth, recession width, probing depth and clinical attachment level in both the groups from baseline to three and six months. However, intergroup comparisons revealed no statistically significant difference. At six months, both groups showed statistically significant improvements in keratinized tissue width and gingival thickness. The gingival thickness of the CAF+CM group increased significantly at three and six months. In terms of root coverage aesthetic score (RES), there was no significant difference observed between the two groups. In terms of patient reported outcome measures (PROMS), patients preferred the CAF+CM technique. Conclusion: Within the limits of the current study, the use of chorion membrane resulted in considerable root coverage and increased gingival thickness. Periodontal regeneration can be facilitated by the distinctive features of the chorion membrane. Coronally advanced flap plus chorion membrane is a novel approach for root coverage procedures.

Captopril is more effective than Perindopril against aluminium chloride induced amyloidogenesis and AD like pathology.

Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role in the pathogenesis and occurrence of Alzheimer's disease. In the present study we evaluated and compared the effect of Captopril and Perindopril against aluminium chloride induced amyloidogenesis and cognitive dysfunction in rats. Wistar rats of both sex were divided randomly into four groups i.e. Group I was served as normal control and treated with normal saline, Group II was administered with AlCl3 (100 mg/kg, p. o.) and Group III and IV received Captopril (30 mg/kg, p. o.) and Perindopril (5 mg/kg, p. o.) respectively 1hr prior to administration of AlCl3. All the doses were given once daily for 42 days. The evaluation of memory function was carried out in Y-maze (spontaneous alternation), radial arm maze (number of correct responses) and elevated plus maze (transfer latency). After behavioral studies, estimation of antioxidant status (brain and serum), amyloid-ß content (brain) and histopathology of brain hippocampus region was done. Administration of AlCl3 for 42 days impaired cognitive dysfunction. Captopril and Perindopril prevented AlCl3 induced cognitive dysfunction by improving spontaneous alternation behavior, number of correct responses and reducing transfer latency. They also increase the antioxidant status, reduce the Aß42 content in the brain and reverse the histopathological changes caused by AlCl3 in hippocampal region. Both Captopril and Perindopril protects against aluminium chloride induced amyloidogenesis and AD like pathology. Captopril is found to be more effective than Perindopril.

Older age and frailty are the chief predictors of mortality in COVID-19 patients admitted to an acute medical unit in a secondary care setting- a cohort study.

BACKGROUND: There is a need for more observational studies across different clinical settings to better understand the epidemiology of the novel COVID-19 infection. Evidence on clinical characteristics of COVID-19 infection is scarce in secondary care settings in Western populations. METHODS: We describe the clinical characteristics of all consecutive COVID-19 positive patients (n = 215) admitted to the acute medical unit at Fairfield General Hospital (secondary care setting) between 23 March 2020 and 30 April 2020 based on the outcome at discharge (group 1: alive or group 2: deceased). We investigated the risk factors that were associated with mortality using binary logistic regression analysis. Kaplan-Meir (KM) curves were generated by following the outcome in all patients until 12 May 2020. RESULTS: The median age of our cohort was 74 years with a predominance of Caucasians (87.4%) and males (62%). Of the 215 patients, 86 (40%) died. A higher proportion of patients who died were frail (group 2: 63 vs group 1: 37%, p < 0.001), with a higher prevalence of cardiovascular disease (group 2: 58 vs group 1: 33%, p < 0.001) and respiratory diseases (group 2: 38 vs group 1: 25%, p = 0.03). In the multivariate logistic regression models, older age (odds ratio (OR) 1.03; p = 0.03), frailty (OR 5.1; p < 0.001) and lower estimated glomerular filtration rate (eGFR) on admission (OR 0.98; p = 0.01) were significant predictors of inpatient mortality. KM curves showed a significantly shorter survival time in the frail older patients. CONCLUSION: Older age and frailty are chief risk factors associated with mortality in COVID-19 patients hospitalised to an acute medical unit at secondary care level. A holistic approach by incorporating these factors is warranted in the management of patients with COVID-19 infection.