Optimized plasmid loading of human erythrocytes for Plasmodium falciparum DNA transfections.

In vitro modification of Plasmodium falciparum genes is the cornerstone of basic and translational malaria research. Achieved through DNA transfection, these modifications may entail altering protein sequence or abundance. Such experiments are critical for defining the molecular mechanisms of key parasite phenotypes and for validation of drug and vaccine targets. Despite its importance, successful transfection remains difficult and is a resource-intensive, rate-limiting step in P. falciparum research. Here, we report that inefficient loading of plasmid into erythrocytes limits transfection efficacy with commonly used electroporation methods. As these methods also require expensive instrumentation and consumables that are not broadly available, we explored a simpler method based on plasmid loading through hypotonic lysis and resealing of erythrocytes. We used parasite expression of a sensitive NanoLuc reporter for rapid evaluation and optimization of each step. Hypotonic buffer composition, resealing buffer volume and composition, and subsequent incubation affected plasmid retention and successful transfection. While ATP was critical for erythrocyte resealing, addition of Ca++ or glutathione did not improve transfection efficiency, with increasing Ca++ concentrations proving detrimental to outcomes. Compared with either the standard electroporation method or a previously reported hypotonic loading protocol, the optimized method yields greater plasmid loading and higher expression of the NanoLuc reporter 48 h after transfection. It also produced significantly faster outgrowth of parasites in transfections utilizing either episomal expression or CRISPR-Cas9 mediated integration. This new method produces higher P. falciparum transfection efficiency, reduces resource requirements and should accelerate molecular studies of malaria drug and vaccine targets.

An Innovative Technique for Assessment of Bone Change, Bite Force, and Retention of the Single-Implant-Supported Mandibular Overdenture: A Clinical Study.

This study is the first study to incorporate a novel approach to single-implant-retained mandibular overdenture with a bar attachment on a single implant in the symphysis region. The use of a single-implant-retained bar overdenture significantly improved patients' chewing efficiency, indicating enhanced overdenture retention and stability. Materials and Methods: Ten maxillary and mandibular completely edentulous patients were enrolled in the study. A complete denture was fabricated for them. On completion, bite force, retention force, and bone change were recorded. Bite force was recorded with the strain gauge, retention force with the force measurement gauge, and bone changes with radiographs. Conclusion: Single-implant-supported bar mandibular overdenture (SISBOD) can be a suitable standard economic option for edentulous mandible and can greatly improve the quality of life of patients.

A neoteric annotation on the advances in combination therapy for Parkinson's disease: nanocarrier-based combination approach and future anticipation. Part II: nanocarrier design and development in focus.

INTRODUCTION: The current treatment modalities available for Parkinson's disease (PD) prove inadequate due to the inherent constraints in effectively transporting bioactive compounds across the blood-brain barrier. The utilization of synergistic combinations of multiple drugs in conjunction with advanced nanotechnology, emerges as a promising avenue for the treatment of PD, offering potential breakthroughs in treatment efficacy, targeted therapy, and personalized medicine. AREAS COVERED: This review provides a comprehensive analysis of the efficacy of multifactorial interventions for PD, simultaneously addressing the primary challenges of conventional therapies and highlighting how advanced technologies can help overcome these limitations. Part II focuses on the effectiveness of nanotechnology for improving pharmacokinetics of conventional therapies, through the synergistic use of dual or multiple therapeutic agents into a single nanoformulation. Significant emphasis is laid on the advancements toward innovative integrations, such as CRISPR/Cas9 with neuroprotective agents and stem cells, all effectively synergized with nanocarriers. EXPERT OPINION: By using drug combinations, we can leverage their combined effects to enhance treatment efficacy and mitigate side effects through lower dosages. This article is meant to give nanocarrier-mediated co-delivery of drugs and the strategic incorporation of CRISPR/Cas9, either as an independent intervention or synergized with a neuroprotective agent.

A neoteric annotation on the advances in combination therapy for Parkinson's disease: nanocarrier-based combination approach and future anticipation. Part I: exploring theoretical insights and pharmacological advances.

INTRODUCTION: Parkinson's disease (PD) is a neurological condition defined by a substantial reduction in dopamine-containing cells in the substantia nigra. Levodopa (L-Dopa) is considered the gold standard in treatment. Recent research has clearly shown that resistance to existing therapies can develop. Moreover, the involvement of multiple pathways in the nigrostriatal dopaminergic neuronal loss suggests that modifying the treatment strategy could effectively reduce this degeneration. AREAS COVERED: This review summarizes the key concerns with treating PD patients and the combinations, aimed at effectively managing PD. Part I focuses on the clinical diagnosis at every stage of the disease as well as the pharmacological treatment strategies that are applied throughout its course. It methodically elucidates the potency of multifactorial interventions in attenuating the disease trajectory, substantiating the rationale for co-administration of dual or multiple therapeutic agents. Significant emphasis is laid on evidence-based pharmacological combinations for PD management. EXPERT OPINION: By utilizing multiple drugs in a combination fashion, this approach can leverage the additive or synergistic effects of these agents, amplify the spectrum of treatment, and curtail the risk of side effects by reducing the dose of each drug, demonstrating significantly greater efficacy.

Evaluation of the Prevalence of White Spot Lesions During Fixed Orthodontic Treatment Among Patients Reporting for Correction of Malocclusion: A Prevalence Study.

BACKGROUND: Despite recent breakthroughs in caries preventive measures, one of the biggest issues clinicians confront is preventing demineralization while undergoing orthodontic therapy. The buildup of plaques around orthodontic brackets over time causes white spot lesions (WSLs). The goal of the present research was to assess the prevalence of WSLs in patients undergoing orthodontic treatment before starting therapy and at six and 12 months into therapy, adopting the visual examination approach. MATERIALS AND METHODS: We looked for WSLs on tooth surfaces gingival to an archwire because this is the area most likely to experience enamel demineralization during orthodontic treatment. The visual assessment was conducted using the following scale at baseline, six months, and 12 months for orthodontic patients: score 0: no demineralization or noticeable white patches on the surface; score 1: mild demineralization with a visible white spot but no surface disruption; score 2: moderate demineralization with a noticeable WSL that has a roughened surface but does not need repair; and score 3: severe demineralization with a noticeable WSL that needs repair. Fisher's exact test was used after a chi-square analysis to determine whether there were any differences between all three categories (six months, 12 months, and control). RESULTS: The frequency of WSL in patients at 12 months of orthodontic treatment was 46.57%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.01), showing that the frequency was greater in patients at 12 months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 11.86% in patients who just started orthodontic treatment. The difference was statistically significant (p = 0.03), showing that the frequency was greater in patients at six months of orthodontic treatment as compared to patients who had just started undergoing orthodontic treatment. The frequency of WSL in patients at six months of orthodontic treatment was 37.34%, while it was 46.57% in patients at 12 months of orthodontic treatment. The frequency was greater in patients at 12 months of orthodontic treatment as compared to patients at six months of orthodontic treatment; however, the difference was non-significant statistically (p = 0.76). CONCLUSION: This clinical investigation revealed that the number of WSLs increased significantly during the first six months of treatment and then increased gradually until the final 12 months. During the first few months of treatment, doctors should assess the patients' dental hygiene habits and, if necessary, take further precautions to prevent demineralization.

Impact of dental and orofacial trauma on oral health-related quality of life in adults: A systematic review.

PURPOSE: Dental and orofacial trauma among the adult population constitutes a major public health problem. The impact is not just physical but also psychological. To analyse the impacts of dental and orofacial trauma on oral health-related quality of life (OHRQoL) in adults and determine whether the 2 variables are closely interlinked. METHODS: This is a systematic review. The terms "dental trauma", "orofacial trauma", "oral health", "oral health related impact life", "OHRQoL", "positive and negative affect scale", "quality of life", "facial injuries", "adults", and "young adults" were researched in the databases of PubMed, ScienceDirect, Scopus and Google Scholar for associated studies up to December 30, 2022. A comprehensive search was designed and the articles were independently screened for eligibility by 2 reviewers. The included studies' author, year of publication, the country where the study was conducted, population demographics (number and age), an instrument used for assessing OHRQoL and the relevant result were recorded and compared. The quality of the evidence was assessed using Joanna Briggs Institute checklist for observational studies. RESULTS: Out of 482 unique records, 3 articles were included for data extraction. Observational studies were included. Two studies did not mention confounding factors. Different scales were used for dental and orofacial trauma and OHRQoL. OHRQoL has a directly proportional relationship with orofacial trauma. Adolescents with orofacial trauma have a significant impact on this value with a prevalence of 88.4%. CONCLUSION: The highest impact on OHRQoL was seen immediately after the diagnosis of an orofacial trauma. The impact increases with the severity of the trauma. Therefore, to promote overall dental and general health, health education initiatives should include information on the causes, prevention, and requirement for prompt responses by the populace in seeking dental intervention.

Pyrolysis of rubber seed pericarp biomass treated with sulfuric acid for the adsorption of crystal violet and methylene green dyes: an optimized process.

In this study, the biomass of rubber seed pericarp was first treated with sulfuric acid and then its activated carbon was formed by the pyrolysis process. As produced acid-treated activated carbon of chosen biomass was then used for the adsorption of crystal violet (CV) and methylene green (MG) from the colored aqueous solution. The adsorbent was exposed to several characterization methods to know its structural and morphological behaviors before and after CV and MG adsorption. The adsorbent was found to be mesoporous having a surface area of 59.517 m2/g. The effect of pH, time, and concentration was assessed while various isotherm and kinetics models were employed to know the adsorption insight. The optimum conditions were at pH 8, within 30 min, 50 mg/L concentration, and 0.06 gm dose. The adsorption data (the maximum adsorption capacity for CV and MG were found to be 302.7 and 567.6 mg/g, respectively) was validated by fitting in a response surface statistical methodology and the positive interactions between the studied factors were found. The adsorption was mainly belonging to the electrostatic attraction of the dye molecules. The study proves that the used adsorbent is economical and an excellent source of treating wastewater.

The novelty of this research work comes from the conversion of the abundant biomass waste namely rubber seed pericarp into sulfonated-rich carbon material by pyrolysis process to be an efficient adsorbent for two structurally different cationic dyes. Furthermore, statistical optimization by using response surface methodology was applied to optimize the adsorption key parameters.

Targeting new N-furfurylated 4-chlorophenyl-1,2,4-triazolepropionamide hybrids as potential 15-lipoxygenase inhibitors supported with in vitro and in silico studies.

Lipoxygenases (LOXs) are a group of enzymes that catalyze the oxidation of polyunsaturated fatty acids and initiate the biosynthesis of secondary metabolites that are involved to control inflammation. In search of new and more potent LOX inhibitors, a series of new 3-(5-(4-chlorophenyl)-4-(2-furylmethyl)-1,2,4-triazole hybrids was prepared and screened for its LOX inhibitory potential. 4-Chlorobenzoic acid (a) was metamorphosed into N-furfuryl-5-(4-chlorophenyl)-4-(2-furylmethyl)-1,2,4-triazole (4) via intermediates like benzoate (1), hydrazide (2) and semicarbazide (3). Finally, triazole (4) was fused with propionamides (6a-o) and transformed it into the aimed derivatives (7a-o). The structural interpretations of the prepared derivatives (7a-o) were accomplished via FTIR, 1H-, 13C-NMR spectroscopy, EI-MS and HR-EI-MS spectrometry. The inhibitory potency of the compounds against soybean 15-LOX was determined by in vitro assay using chemiluminescence method. Compounds 7a and 7f exhibited potent LOX inhibitory profiles with IC50 21.83 ± 0.56 and 25.72 ± 0.51 µM, whereas 7d and 7e showed comparable inhibitory potential with IC50 values of 34.52 ± 0.39 and 39.12 ± 0.46 µM, respectively. Compounds 7a, 7f, 7d and 7e exhibited 65.58 ± 1.4%, 54.72 ± 1.3%, 58.52 ± 1.2% and 63.56 ± 1.4% blood mononuclear cells viability, respectively. Density functional theory and molecular docking studies further strengthened the studies of the synthesized compounds and these derivatives perceived to be potential 'lead' compounds in drug discovery as anti-LOX.Communicated by Ramaswamy H. Sarma.

Signalling Pathways Involved in Microglial Activation in Alzheimer's Disease and Potential Neuroprotective Role of Phytoconstituents.

Alzheimer's disease (AD) is a commonly reported neurodegenerative disorder associated with dementia and cognitive impairment. The pathophysiology of AD comprises Aß, hyperphosphorylated tau protein formation, abrupt cholinergic cascade, oxidative stress, neuronal apoptosis, and neuroinflammation. Recent findings have established the profound role of immunological dysfunction and microglial activation in the pathogenesis of AD. Microglial activation is a multifactorial cascade encompassing various signalling molecules and pathways such as Nrf2/NLRP3/NF-kB/p38 MAPKs/ GSK-3ß. Additionally, deposited Aß or tau protein triggers microglial activation and accelerates its pathogenesis. Currently, the FDA-approved therapeutic regimens are based on the modulation of the cholinergic system, and recently, one more drug, aducanumab, has been approved by the FDA. On the one hand, these drugs only offer symptomatic relief and not a cure for AD. Additionally, no targeted-based microglial medicines are available for treating and managing AD. On the other hand, various natural products have been explored for the possible anti-Alzheimer effect via targeting microglial activation or different targets of microglial activation. Therefore, the present review focuses on exploring the mechanism and associated signalling related to microglial activation and a detailed description of various natural products that have previously been reported with anti-Alzheimer's effect via mitigation of microglial activation. Additionally, we have discussed the various patents and clinical trials related to managing and treating AD.

Ocular Toxicity of Ethambutol During Both Intensive and Continuation Phases of Anti-Tubercular Therapy in Children.

OBJECTIVE: The study was conducted to evaluate the ocular toxicity of ethambutol given in both intensive and continuation phases of treatment in children with drug-sensitive tuberculosis. METHODS: A prospective study of 94 eyes from 47 patients receiving an ethambutol-containing regimen was conducted between 1 December, 2018 and 31 August, 2020. Visual acuity, visual field, visual evoked response (VER), contrast sensitivity, colour perception, and retinal nerve fiber layer (RNFL) thickness [using optical coherence tomography (OCT)] were tested for each patient before, during, and after the treatment. RESULTS: On follow-up, visual acuity, color vision, contrast sensitivity, fundus, and visual fields were not affected in any of the patients. There was no statistically significant increase in the mean latency of the P(100) wave at any point in time. On OCT, no significant loss of mean RNFL thickness was detected. CONCLUSIONS: Ethambutol is safe to use up to a dose of 20 mg/kg/day throughout the entire course of anti-tubercular therapy in children with drug-sensitive tuberculosis.

A technical note on emerging combination approach involved in the onconanotherapeutics.

Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.

4-Phthalimidobenzenesulfonamide Derivatives as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: DFTs, 3D-QSAR, ADMET, and Molecular Dynamics Simulation.

INTRODUCTION: Alzheimer's disease is a form of dementia which affects majority of the people. It is characterized by memory loss and other cognitive function disabilities and is one of the most challenging neurodegenerative disorders to treat because of its progressive nature. The disease affects millions of people all around the world, and the number of those affected is expanding every day. In the previous study, the 4-phthalimidobenzenesulfonamide derivatives were synthesized as AChE and BChE inhibitors, and here, we were aiming to further reporting in silico studies of these compounds for efficient drug discovery process and to find out the potential lead compounds. METHODS: In silico characterization included density functional theory (DFT) studies, 3D-QSAR, ADMET properties, molecular docking, and molecular dynamic simulations. The geometries of all derivatives were optimized using B3LYP method and 6-311G basis set. RESULTS: The findings of the current study revealed that 4-phthalimidobenzenesulfonamide derivatives exhibited a reactive electronic property which is essential for anticholinesterase activity. Moreover, optimized structures were subjected to molecular docking studies with targeted protein. The compounds 2c and 2g showed excellent binding score of -37.44 and -33.67 kJ/mol with BChE and AChE, respectively, and exhibited strong binding affinity. The potent derivatives produced stable complex with amino acid residues of active pocket of both BChE and AChE. The stability of protein-ligand complexes was determined by molecular dynamic simulation studies, and results were found in correlation with molecular docking findings. CONCLUSION: Findings of the current study suggested that these derivatives are potent inhibitors of cholinesterase enzyme.

Assessing p-tolyloxy-1,3,4-oxadiazole acetamides as lipoxygenase inhibitors assisted by in vitro and in silico studies.

The underlying correlation between the inflammation, innate immunity and cancer is extensively familiar and linked through a process mediated by three enzymes; cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP450). The ever increase in the reported side effects of the antiinflammatory drugs against the targeted enzymes and the resistance developed afterwards compels the researchers to synthesize new effective molecules with safer profile. On the basis of these facts, our ongoing research on 1,3,4-oxadiazole derivatives deals with the synthesis of a new series of N-alkyl/aralky/aryl derivatives of 5-((p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-ylthio)acetamide (6a-o) which were developed by the sequential conversion of p-tolyloxyacetic acid (a) into ester (1) hydrazide (2) and 5-(p-tolyloxymethyl)-4H-1,3,4-oxadiazole-2-thiol (3). The designed compounds (6a-o) were acquired by the reaction of 1,3,4-oxadiazole (3) with numerous electrophiles (5a-o) in KOH. The synthesized analogues (6a-o) were characterized by FTIR, 1H-, 13C NMR spectroscopy, EI-MS and HR-EI-MS spectrometry, and were further assessed for their inhibitory potential against the soybean 15-LOX enzyme. The results showed excellent inhibitory potential of the compounds against the said enzyme, specifically 6o, 6b, 6n and 6e with inhibitory values (IC50 ± SEM) of 21.5 ± 0.76, 24.3 ± 0.45, 29.1 ± 0.65 and 31.3 ± 0.78 µM, respectively. These compounds displayed < 55 % blood mononuclear cells (MNCs) cellular viability as measured by MTT assay at 0.25 mM concentration. Other compounds demonstrated moderate inhibitory activities with IC50 values in the range of 33.2 ± 0.78 to 96.3 ± 0.73 µM and exhibited little cellular viability against MNCs except 6i, 6j, 6 m and 6 k that showed 61-79 % cellular viability. It was observed that most of the compounds (6o, 6b, 6n, 6e) were found more toxic towards MNCs at studied concentration of 0.25 mM. SAR studies revealed that the positions and nature of substituents accompanying phenyl ring have great influence on 15-LOX inhibitory activity. In the most active compound 6o, the amino acids Asp768 and Val126 were involved in hydrogen bonding, Thr529 was linked with π-anion interaction and π-sulphur interaction was displayed with Tyr525 and two π-alkyl interactions were formed with the benzene ring and amino acid residues Pro530 and Arg533. The in silico pharmacokinetics profiles and density functional theory calculations of the compounds further supported the in vitro findings. Further work on the synthesis of more oxadiazole derivatives is in progress in search for potential 'leads' for the drug discovery as LOX inhibitors.

Fabrication of polyamide-12/cement nanocomposite and its testing for different dyes removal from aqueous solution: characterization, adsorption, and regeneration studies.

Polyamide-12/Portland cement nanocomposite was prepared by using the exfoliated adsorption method. The fabricated nanocomposite was applied first time to remove Congo red (CR), brilliant green (BG), methylene blue (MB), and methyl red (MR) from the synthetic wastewater. The polymer nanocomposite was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental mapping, Brunauer-Emmett-Teller surface area analysis, and X-ray diffraction. The adsorption was rapid and all the studied dyes were absorbed on the surface of the polymer nanocomposite in 90 min. The point of zero charge was found at pH 5 and the factors such as pH, time, and temperature were found to affect the adsorption efficiency. Freundlich isotherm and pseudo-second-order models well-fitted the adsorption isotherm and kinetics data, respectively. The calculated maximum adsorption capacity was 161.63, 148.54, 200.40, and 146.41 mg/g for CR, BG, MB, and MR, respectively. The mode of the adsorption process was endothermic, spontaneous, and physical involving electrostatic attraction. On an industrial scale, the high percentage of desorption and slow decrease in the percentage of adsorption after every five regeneration cycles confirm the potential, practicality, and durability of the nanocomposite as a promising and advanced adsorbent for decolorization of colored wastewater.

Pathogenic mechanisms and therapeutic promise of phytochemicals and nanocarriers based drug delivery against radiotherapy-induced neurotoxic manifestations.

Radiotherapy is one of the extensively used therapeutic modalities in glioblastoma and other types of cancers. Radiotherapy is either used as a first-line approach or combined with pharmacotherapy or surgery to manage and treat cancer. Although the use of radiotherapy significantly increased the survival time of patients, but its use has been reported with marked neuroinflammation and cognitive dysfunction that eventually reduced the quality of life of patients. Based on the preclinical and clinical investigations, the profound role of increased oxidative stress, nuclear translocation of NF-kB, production of proinflammatory cytokines such as TNF-α, IL-6, IL-ß, increased level of MMPs, increased apoptosis, reduced angiogenesis, neurogenesis, and histological aberrations in CA1, CA2, CA3 and DG region of the hippocampus have been reported. Various pharmacotherapeutic drugs are being used as an adjuvant to counteract this neurotoxic manifestation. Still, most of these drugs suffer from systemic adverse effect, causes interference to ongoing chemotherapy, and exhibit pharmacokinetic limitations in crossing the blood-brain barrier. Therefore, various phytoconstituents, their nano carrier-based drug delivery systems and miRNAs have been explored to overcome the aforementioned limitations. The present review is focused on the mechanism and evidence of radiotherapy-induced neuroinflammation and cognitive dysfunction, pathological and molecular changes in the brain homeostasis, available adjuvants, their limitations. Additionally, the potential role and mechanism of neuroprotection of various nanocarrier based natural products and miRNAs have been discussed.

Efficacy of Knee Taping in addition to a Supervised Exercise Protocol to Manage Pain and Functional Status in Individuals with Patellofemoral Osteoarthritis: A Randomized, Controlled Clinical Trial.

Purpose: This study aimed to investigate the effect of knee taping in addition to a supervised exercise protocol on the pain intensity and functional status of individuals with patellofemoral osteoarthritis (PF OA). Methods: The study was based on a randomized, controlled pretest-posttest experimental group design. Following an initial screening, forty people with PF OA (mean age 55, range 40-60) were randomly assigned to one of two groups, Group A or Group B (n = 20 each). Group A underwent knee taping and participated in a supervised exercise program, whereas Group B only participated in a supervised exercise program. For four weeks, both groups received their prescribed treatment five consecutive days each week. At baseline (day 1 preintervention) and 4 weeks postintervention, the visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were obtained. To compare the effect of stipulated interventions within and between groups, paired and unpaired t tests were performed, with the level of significance set at p < 0.05. Results: When comparing the outcome scores at 4 weeks postintervention with baseline scores, the within-group analysis revealed significant mean differences for the outcomes within groups A (VAS: MD = -3.08-0.76; T = 9.70; p < 0.05 and WOMAC: MD = -7.05-0.81; T = 11.11; p < 0.05) and B (WOMAC: MD = -1.6-0.17; T = 2.35; p < 0.05), but a nonsignificant mean difference for the outcomes of VAS within group B (∆MD = 0.08 ± 0.03; T = -0.56; p > 0.05). Similarly, when the score of VAS (MD = -2.73-1.29; T = -9.17; p < 0.05) and WOMAC (MD = -5.95-1.63; T = -5.86; p < 0.05) were compared at 4 weeks postintervention, there was a significant mean difference between groups A and B. Conclusions: In people with patellofemoral osteoarthritis, combining knee taping with a supervised exercise protocol was more effective than the supervised exercise protocol alone in relieving pain and enhancing functional status.

An Overview and Therapeutic Promise of Nutraceuticals Against Sports-Related Brain Injury.

Sports-related traumatic brain injury (TBI) is one of the common neurological maladies experienced by athletes. Earlier, the term 'punch drunk syndrome' was used in the case TBI of boxers and now this term is replaced by chronic traumatic encephalopathy (CTE). Sports-related brain injury can either be short-term or long-term. A common instance of brain injury encompasses subdural hematoma, concussion, cognitive dysfunction, amnesia, headache, vision issue, axonopathy, or even death, if it remains undiagnosed or untreated. Further, chronic TBI may lead to pathogenesis of neuroinflammation and neurodegeneration via tauopathy, the formation of neurofibrillary tangles, and damage to the blood-brain barrier, microglial, and astrocyte activation. Thus, altered pathological, neurochemical, and neurometabolic attributes lead to the modulation of multiple signaling pathways and cause neurological dysfunction. Available pharmaceutical interventions are based on one drug one target hypothesis and are thereby unable to cover altered multiple signaling pathways. However, in recent times, pharmacological intervention of nutrients and nutraceuticals have been explored as they exert a multifactorial mode of action and maintain over homeostasis of the body. There are various reports available showing the positive therapeutic effect of nutraceuticals in sport-related brain injury. Therefore, in the current article, we have discussed the pathology, neurological consequence, sequelae, and perpetuation of sports-related brain injury. Further, we have discussed various nutraceutical supplements as well as available animal models to explore the neuroprotective effect/ upshots of these nutraceuticals in sports-related brain injury.

Nutraceuticals and their Derived Nano-Formulations for the Prevention and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is one of the common chronic neurological disorders and associated with cognitive dysfunction, depression and progressive dementia. The presence of ß-amyloid or senile plaques, hyper-phosphorylated tau proteins, neurofibrillary tangle, oxidative-nitrative stress, mitochondrial dysfunction, endoplasmic reticulum stress, neuroinflammation and derailed neurotransmitter status are the hallmarks of AD. Currently, donepezil, memantine, rivastigmine and galantamine are approved by the FDA for symptomatic management. It is well-known that these approved drugs only exert symptomatic relief and possess poor patient-compliance. Additionally, various published evidence showed the neuroprotective potential of various nutraceuticals via their antioxidant, anti-inflammatory and anti-apoptotic effects in the preclinical and clinical studies. These nutraceuticals possess a significant neuroprotective potential and hence, can be a future pharmacotherapeutic for the management and treatment of AD. However, nutraceuticals suffer from certain major limitations such as poor solubility, low bioavailability, low stability, fast hepatic- metabolism and larger particle size. These pharmacokinetic attributes restrict their entry into the brain via the blood-brain barrier. Therefore, to overcome such issues, various nanoformulations of nutraceuticals have been developed, that allow their effective delivery into the brain owing to reduced particle size, increased lipophilicity, increased bioavailability and avoidance of fast hepatic metabolism. Thus, in this review, we have discussed the etiology of AD, focusing on the pharmacotherapeutics of nutraceuticals with preclinical and clinical evidence, discussed pharmaceutical limitations and regulatory aspects of nutraceuticals to ensure safety and efficacy. We have further explored various nanoformulations of nutraceuticals as a novel approach to overcome the existing pharmaceutical limitations and for effective delivery into the brain.

Compendium of Conventional and Targeted Drug Delivery Formulation Used for the Treatment and Management of the Wound Healing.

Wound healing is a complex and dynamic phenomenon that involves the restoration of normal physiology and functioning of injured tissue. The process of wound healing is primarily regulated by various cytokines, inflammatory mediators, and growth factors at the molecular level. Any intervention in the normal wound healing process leads to further tissue damage, which in turn leads to delayed wound healing. Several natural, synthetic drugs and their combinations were used to restore and accelerate the wound healing process. However, the conventional delivery carriers were not much effective, and thus, nowadays, nanocarriers are gaining much popularity since they are playing a pivotal role in drug delivery. Since nanocarriers have their own applicability and benefits (enhance the bioavailability, site-specific targeting) so, they can accelerate wound healing more efficiently. This review briefly discussed about the various events that take place during the wound healing process with emphasis on various natural, synthetic, and combination drug therapy used for accelerating wound healing and the role of nanotechnology-based approaches in chronic wound healing.

Recent Advancement of Pyrazole Scaffold Based Neuroprotective Agents: A Review.

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC50 values (in mM as well as in µM), recent patents, and a brief history as neuroprotective agents.