Recent Advances in Delivery of Peptide and Protein Therapeutics to the Brain.

The classes of neuropharmaceuticals known as proteins and peptides serve as diagnostic tools and are involved in specific communication in the peripheral and central nervous systems. However, due to tight junctions resembling epithelial cells found in the blood-brain barrier (BBB) in vivo, they are typically excluded from transport from the blood to the brain. The drugs having molecular weight of less than 400 Dalton are able to cross the BBB via lipid-mediated free diffusion. However, large molecule therapeutics are devoid of these characteristics. As an alternative, these substances may be carried via chimeric peptide drug delivery systems, and assist in transcytosis through BBB with the aid of linker strategies. With their recent developments, several forms of nanoparticles, including poly (ethylene glycol)-poly(ε-caprolactone) copolymers, nanogels, liposomes, nanostructured lipid carriers, poly (D, L-lactide-co-glycolide) nanoparticles, chitosan, and solid lipid nanoparticles, have also been considered for their therapeutic applications. Moreover, the necessity for physiologic optimization of current drug delivery methods and their carriers to deliver therapeutic doses of medication into the brain for the treatment of various neurologic illnesses has also been emphasized. Therapeutic use of proteins and peptides has no neuroprotective impact in the absence of all these methods. Each tactic, however, has unique drawbacks and considerations. In this review, we discuss different drug delivery methods for therapeutic distribution of pharmaceuticals, primarily neuroproteins and neuropeptides, through endothelial capillaries via blood-brain barrier. Finally, we have also discussed the challenges and future perspective of protein and peptide therapeutics delivery to the brain. SIGNIFICANCE STATEMENT: Very few reports on the delivery of therapeutic protein and peptide nanoformulations are available in the literature. Herein, we attempted to discuss these nanoformulations of protein and peptide therapeutics used to treat brain diseases.

COVID-19 Virus Structural Details: Optical and Electrochemical Detection.

The increasing viral species have ruined people's health and the world's economy. Therefore, it is urgent to design bio-responsive materials to provide a vast platform for detecting a different family's passive or active virus. One can design a reactive functional unit for that moiety based on the particular bio-active moieties in viruses. Nanomaterials as optical and electrochemical biosensors have enabled better tools and devices to develop rapid virus detection. Various material science platforms are available for real-time monitoring and detecting COVID-19 and other viral loads. In this review, we discuss the recent advances of nanomaterials in developing the tools for optical and electrochemical sensing COVID-19. In addition, nanomaterials used to detect other human viruses have been studied, providing insights for developing COVID-19 sensing materials. The basic strategies for nanomaterials develop as virus sensors, fabrications, and detection performances are studied. Moreover, the new methods to enhance the virus sensing properties are discussed to provide a gateway for virus detection in variant forms. The study will provide systematic information and working of virus sensors. In addition, the deep discussion of structural properties and signal changes will offer a new gate for researchers to develop new virus sensors for clinical applications.

Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.

BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.

Multimetal exposure: Challenges in diagnostics, prevention, and treatment.

Extensive use of heavy metals has posed a serious concern for ecosystem and human too. Heavy metals are toxic in nature and their accumulation in human body causes serious disorders such as neurological disease, cardiac disease, gastrointestinal problems, skin disorders, reproductive disease, lungs diseases, and so on. Furthermore, heavy metals not only affect the human health but also have a negative impact on the economy. In the current review, we have elaborated the impact of heavy metal exposure on human health and socioeconomics. We have discussed the molecular mechanism involved in the heavy metal-induced human disorders such as oxidative stress, neuroinflammation, and protein misfolding. Finally, we discussed the preventive measure and treatment strategy that could counter the negative effects of heavy metal intoxications. In conclusion, there is a substantial correlation between heavy metals and the onset and advancement of several health issues. Chelation treatment could be a useful tactic to lessen the toxic metal load and the difficulties that come with it.

Enhancing productivity and sustainability of ravine lands through horti-silviculture and soil moisture conservation: A pathway to land degradation neutrality.

Ravine lands are the worst type of land degradation affecting soil quality and biodiversity. Crop production in such lands is impossible without adopting proper conservation measures. In-situ moisture conservation techniques could play an instrumental role in restoring ravine lands by improving soil moisture. We hypothesized that restoring ravine land through a combination of tree planting, fruit crop cultivation, and in-situ moisture conservation practice would result in significant improvements in productivity, profitability, and soil fertility. An experiment was conducted involving the combination of Malabar Neem (Melia dubia) and Dragon fruit (Hylocereus undatus) in conjunction with in-situ soil moisture conservation measures specifically involving half-moon structures (HM). The experiment was conducted under randomized block design (RBD) comprising eight treatments. These treatments include sole Melia cultivation (MD 3m × 3m), sole cultivation of dragon fruit (DF 3m × 3m), silviculture system (MDF-3m × 3m), horti-silviculture system with larger spacing (MDF-4m × 4m), sole Melia cultivation with in-situ moisture conservation (MDH-3m × 3m), sole Dragon fruit cultivation with in-situ moisture conservation (DFH-3m × 3m), horti-silviculture system of Melia and Dragon fruit with in-situ moisture conservation (MDFH-3m × 3m), and horti-silviculture system with larger spacing and in-situ moisture conservation (MDFH-4m × 4m). Each treatment was replicated thrice to evaluate their impact on productivity, profitability, soil fertility, and carbon sequestration for 8 years (2016-2023). The results revealed that the horti-silviculture system (MDFH-3 × 3 m) exhibited the highest total tree biomass and total carbon sequestration with an increase of 183.2% and 82.8% respectively, compared to sole Melia cultivation without HM and sole Melia with HM. Furthermore, sole Melia with HM augmented soil nutrients (N, P, K, and SOC) by 74.4%, 66.4%, 35.2%, and 78.3%, respectively, compared to control (no planting), with performance at par with MDFH-3 × 3 m. Similarly, sole Melia with HM enhanced SOC stock and SOC sequestration rate by 79.2% and 248% over control. However, it was found at par with MDFH-3 × 3 m. The horti-silviculture system (MDFH-3 × 3 m) consistently produced the highest fruit yield throughout the years surpassing other treatments. This treatment increased the average dragon fruit yield by 115.3% compared to sole dragon fruit without HM. Hence, the adoption of the horti-silviculture system (MDFH-3 × 3 m) could be a promising strategy for achieving enhanced environmental and economic benefits in ravine lands. Therefore, dragon fruit based horti-silviculture system (MDFH-3 × 3 m) could be recommended for restoration of ravine lands, improving land productivity, and mitigating impact of soil erosion particularly in Western India or similar agro-climatic regions of the world.

Understanding zebrafish sleep and wakefulness physiology as an experimental model for biomedical research.

Sleep is a globally observable fact, or period of reversible distracted rest, that can be distinguished from arousal by various behavioral criteria. Although the function of sleep is an evolutionarily conserved behavior, its mechanism is not yet clear. The zebrafish (Danio rerio) has become a valuable model for neurobehavioral studies such as studying learning, memory, anxiety, and depression. It is characterized by a sleep-like state and circadian rhythm, making it comparable to mammals. Zebrafish are a good model for behavioral studies because they share genetic similarities with humans. A number of neurotransmitters are involved in sleep and wakefulness. There is a binding between melatonin and the hypocretin system present in zebrafish. The full understanding of sleep and wakefulness physiology in zebrafish is still unclear among researchers. Therefore, to make a clear understanding of the sleep/wake cycle in zebrafish, this article covers the mechanism involved behind it, and the role of the neuromodulator system followed by the mechanism of the HPA axis.

The Role of Mitophagy in Various Neurological Diseases as a Therapeutic Approach.

Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.

Crosstalk between phytochemicals and inflammatory signaling pathways.

Novel bioactive constituents from natural sources are actively being investigated. The phytochemicals in these phenolic compounds are believed to have a variety of beneficial effects on human health. Several phenolic compounds have been found in plants. The antioxidant potential of phenols has been discussed in numerous studies along with their anti-inflammatory effects on pro-inflammatory cytokine, inducible cyclooxygenase-2, and nitric oxide synthase. Through current study, an attempt is made to outline and highlight a wide variety of inflammation-associated signaling pathways that have been modified by several natural compounds. These signaling pathways include nuclear factor-kappa B (NF-кB), activator protein (AP)-1, protein tyrosine kinases (PTKs), mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors, tyrosine phosphatidylinositol 3-kinase (PI3K)/AKT, and the ubiquitin-proteasome system. In light of the influence of natural substances on signaling pathways, their impact on the production of inflammatory mediator is highlighted in this review.

Drug-herb combination therapy in cancer management.

Cancer is the second leading cause of fatality all over the world. Various unwanted side effects are being reported with the use of conventional chemotherapy. The plant derived bioactive compounds are the prominent alternative medicinal approach for reduction of chemotherapy associated side effects. The data is collected from Pubmed, Sci-hub, Google scholar, and Research gate were systematically searched up to year 2020. Several herbal drugs have been investigated and found with grateful anti-cancer potentials hence, it can be used in combination with chemotherapy for the depletion of associated side-effects. Herbal drugs and their extracts contain a mixture of active ingredients, which show interactions within themselves and along with chemotherapeutic agents to show either synergistic or antagonistic therapeutic effects. Therefore, it is necessary to develop alternative treatment to control chemotherapy associated side-effects. In this review, we discussed some of the significant chemical compounds, which could be efficient against cancer. This review focuses on the different herbal drugs that play an important role in the treatment of cancer and its associated side-effects. This study aimed to evaluate the efficacy of herbal treatment in combination with chemotherapy for cancer treatment.

Quercetin ameliorates lipopolysaccharide-induced neuroinflammation and oxidative stress in adult zebrafish.

BACKGROUND: Quercetin is a natural flavonoid that is known to have numerous pharmacological activities such as antioxidative, anti-inflammatory, and neuroprotective effects against various neurological disorders. Lipopolysaccharide (LPS) is a potent endotoxin, reported causing several neurological disorders. AIM: The present study was designed to investigate the possibility that quercetin ameliorates LPS induced oxidative stress and neuroinflammation in adult zebrafish. MATERIALS AND METHODS: Zebrafish (weighing 470-530 mg) were treated with a single injection of LPS (1 mg/kg) intraperitoneally (i.p.) followed by post-treatment with quercetin (50 and 100 mg/kg; i.p.) for 7 days. After sacrificing brain was harvested and subjected for biochemical, molecular, and histological analyses. RESULTS: Results revealed post-treatment with quercetin was able to ameliorate the behavioral abnormalities as in novel tank diving test- time spent in the top zone (TSTZ), and the number of entries in the top zone was significantly (p < 0.01) more as compared to time spent in the bottom zone (TSBZ). In the light-dark chamber test- time spent in the light zone (TSLZ), and the number of entries in the light zone were significantly (p < 0.01) more as compared to time spent in the dark compartment (TSDC). Additionally, results of histopathology (H & E stain) studies showed less disruption in neuronal cells as compared to the LPS treated group. Moreover, the results of the molecular analysis revealed that quercetin treatment significantly (p < 0.01) decrease TNF-α and IL-1ß levels as compared to LPS treated animals. Further, results of the biochemical analysis reveal that quercetin significantly (p < 0.01) reduces the level of LPO, nitrite, AChEs and increases anti-oxidant GSH. CONCLUSION: Quercetin treatment helps to prevent oxidative damage and neuroinflammation in LPS treated adult zebrafish.

Zebrafish an experimental model of Huntington's disease: molecular aspects, therapeutic targets and current challenges.

Huntington disease (HD) is a lethal autosomal dominant neurodegenerative disease whose exact causative mechanism is still unknown. It can transform from one generation to another generation. The CAG triplet expansion on polyglutamine (PolyQ) tract on Huntingtin protein primarily contributes in HD pathogenesis. Apart from this some another molecular mechanisms are also involved in HD pathology such as loss of Brain derived neurotrophic factor in medium spiny neurons, mitochondrial dysfunction, and alterations in synaptic plasticity are briefly discussed in this review. However, several chemicals (3-nitropropionic acid, and Quinolinic acid) and genetic (mHTT-ΔN17-97Q over expression) experimental models are used to explore the exact pathogenic mechanism and finding of new drug targets for the development of novel therapeutic approaches. The zebrafish (Danio rerio) is widely used in in-vivo screening of several central nervous system (CNS) diseases such as HD, Alzheimer's disease (AD), Parkinson's disease (PD), and in memory deficits. Thus, this makes zebrafish as an excellent animal model for the development of new therapeutic strategies against various CNS disorders. We had reviewed several publications utilizing zebrafish and rodents to explore the disease pathology. Studies suggested that zebrafish genes and their human homologues have conserved functions. Zebrafish advantages and their characteristics over the other experimental animals make it an excellent tool for the disease study. This review explains the possible pathogenic mechanism of HD and also discusses about possible treatment therapies, apart from this we also discussed about possible potential therapeutic targets which will helps in designing of novel therapeutic approaches to overcome the disease progression.  Diagrammatic depiction shows prevention of HD pathogenesis through attenuation of various biochemical alterations.

Rare case of concomitant juxtarenal aortic aneurysm and type 1 Inferior Vena Cava duplication: -intraoperative challenges to avoid catastrophe.

Duplication of the inferior vena cava is a rare congenital anomaly, with an incidence of 0.2-3%. Despite being asymptomatic, anomalies of IVC are important in aortoiliac and retroperitoneal surgeries. Preoperative CT imaging is essential to identify any IVC anomaly and to prevent unexpected hemorrhage during surgery. Here, we report a case of a juxtarenal abdominal aortic aneurysm in which we encountered a type I IVC duplication anomaly intraoperatively while performing transperitoneal aneurysmorrhaphy and took precautions to avoid any iatrogenic injuries to either of the two trunks or the pre-aortic trunk of the anomalous duplicate IVC.

A duplicação da veia cava inferior (VCI) é uma anomalia congênita rara com incidência de 0,2 a 3%. Apesar de assintomáticas, anomalias da VCI são importantes em cirurgias aortoilíacas e retroperitoneais. A imagem da tomografia pré-operatória é essencial para identificar qualquer anomalia de VCI e para evitar hemorragia inesperada durante a cirurgia. Relatamos um caso de aneurisma de aorta abdominal justarrenal, no qual encontramos uma anomalia de duplicação de VCI do tipo 1 intraoperatório enquanto realizávamos correção cirúrgica de aneurisma transperitoneal. Por isso, tomamos a precaução para evitar qualquer lesão iatrogênica nos dois troncos e no tronco pré-aórtico de VCI duplicada anômala.

Prevalence of growth hormone deficiency in middle-age adults recovering from stroke.

Objective: The prevalence of chronic growth hormone deficiency (GHD) and its association with other hormonal deficiencies was determined in middle-aged patients post-stroke with and without consideration of body mass index (BMI).Methods: Clinical records were reviewed to determine pituitary function at least 3 months post-stroke. Patients with a history of endocrine anomalies were excluded. GHD was determined by utilizing standard peak GH cutoffs following the glucagon stimulation test. A secondary analysis was conducted with stricter BMI-adjusted cutoffs. The accuracy of IGF-1 in predicting GHD was also examined.Results: GHD was diagnosed in 54% of patients (≥5.0 µg/L), with 32% falling into the severe (≤3 µg/L) category. Patients with GHD had lower levels of FSH, T3, LH, and SHBG. Analyzes of BMI-adjusted GH levels, revealed that 14% of patients were GHD. These patients had higher prolactin. IGF-1 values were not predictive of GHD. Latency to be admitted to post-acute rehabilitation was greater in patients with GHD.Conclusions: Evidence suggests patients with stroke may be at risk for developing GHD. GHD was associated with decreased levels of other hormones. Co-morbidities for stroke and neuroendocrine dysfunction overlap and may have implications for recovery following stroke.

Topical application of nanoparticles integrated supramolecular hydrogels for the potential treatment of seborrhoeic dermatitis.

The current application was aimed to evaluate the therapeutic potential of selenium and ketoconazole nanoparticles loaded hyaluronic acid gel against seborrhoeic dermatitis (SD). Amalgamation of ketoconazole (antifungal medication) and selenium (pro-oxidant) in an optimized formulation setting may help in the treatment of SD. In this study, selenium and ketoconazole nanoparticles loaded hyaluronic acid (HA) hydrogel was prepared by mechanical mixing followed by sonication. Results of the optimized batch showed a mean particle size of 121 ± 12 nm for ketoconazole and 51 ± 7 nm for selenium. SEM and TEM study revealed the prepared nanoparticles are of nanoscale dimension, with smooth spherical outline. Finally, the optimized nanoparticles were incorporated into HA hydrogel. Hydrogel exhibits desirable physical, mechanical and rheological characteristics appropriate for topical application. Optimized gel formulation exhibited an enhanced permeability with better antifungal, and anti-inflammatory activities, compared with the plain drug suspension. The optimized hydrogel with ketoconazole and selenium in nanotemplate could offer a potential strategy for the treatment of SD.

Nicotinamide reverses behavioral impairments and provides neuroprotection in 3-nitropropionic acid induced animal model ofHuntington's disease: implication of oxidative stress- poly(ADP- ribose) polymerase pathway.

Huntington's disease (HD) is characterized by cognitive and psychiatric impairment caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress is the main pathogenic factor in HD. The current study aims to determine the possible neuroprotective effects of nicotinamide on 3-nitropropionic acid (3-NP) induced HD. Male Wistar albino rats were divided into six groups. Group I was the vehicle-treated control, group II received 3-NP (20 mg/kg, intraperitoneally (i.p.) for 4 days, group III received nicotinamide (500 mg/kg, i.p.). The remaining groups received a combination of 3-NP plus nicotinamide 100, 300 or 500 mg/kg, i.p. respectively for 8 days. Afterward, the motor function and hind paw activity in the limb withdrawal were tested; rats were then euthanized for biochemical and histopathological analyses. Treatment of rats with 3-NP altered the motor function, elevated oxidative stress and caused significant histopathological changes in the brain. The treatment of rats with nicotinamide (100, 300 and 500 mg/kg) improved the motor function tested by locomotor activity test, movement analysis, and limb withdrawal test, which was associated with decreased oxidative stress markers (malondialdehyde, nitrites) and increased antioxidant enzyme (glutathione) levels. In addition, nicotinamide treatment decreased lactate dehydrogenase and prevented neuronal death in the striatal region. Our study, therefore, concludes that antioxidant drugs like nicotinamide might slow progression of clinical HD and may improve the motor functions in HD patients. To the best of our knowledge, this study is the first to explore the neuroprotective effects of nicotinamide on 3-NP-induced HD.

The influence of post-acute rehabilitation length of stay on traumatic brain injury outcome: a retrospective exploratory study.

OBJECTIVE: Data regarding length of stay (LOS) in a rehabilitation programme after traumatic brain injury (TBI) are limited. The goal of this study was to examine the effect of LOS and disability on outcome following TBI. METHODS: Records from patients in a multidisciplinary rehabilitation programme at least 3 months after TBI were analysed retrospectively to study the influence of LOS on functional outcome at different levels of disability. Functional status was determined by the Mayo-Portland Adaptability Inventory (MPAI) and the Community Integration Questionnaire (CIQ). Patients were further grouped by time since injury of 3-12 months or over 1 year. RESULTS: Those with a mild and moderate disabilities and over 1 year chronicity showed improvements after 90 days of rehabilitation. Patients with a severe disability and over 1 year chronicity required at least 180 days to show improvements. Moderately and severely disabled patients with an injury chronicity of 3-12 months showed improvements in the MPAI after 90 days. However, further improvement was observed after 180 days in the severely disabled group. CONCLUSIONS: Results suggest that both, level of disability and injury chronicity, should be considered when determining LOS. Data also show an association between LOS and changes in the MPAI and CIQ.

In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery.

The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 ± 23 versus 105.1 ± 12 µg/ml and SDRPL (1:1) 306.4 ± 20 versus 105.1 ± 12 µg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 ± 25 versus 54.31 ± 18 µg/ml), faster T max (two versus four hours), and enhanced area under the curve (AUC0-∞) (406.92 ± 18 versus 147.72 ± 15 µg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin.

Development of Novel Polymer-Lipid Hybrid Nanoparticles of Tamoxifen: In Vitro and In Vivo Evaluation.

This study was undertaken to develop and investigate the effect of tamoxifen polymer-lipid hybrid nanoparticles (Tmx-PLN) on its oral bioavailability and efficacy in the 7,12-dimethylbenzanthracene (DMBA)-induced breast cancer model. Modified solvent emulsification-evaporation method was optimized to obtain Tmx-PLN, composed of chitosan and lecithin, of 169.66 ± 4.84 nm particle size. The PLN exhibited prolonged in vitro release in phosphate-buffered saline. Further, PLN displayed enhanced oral bioavailability with considerable increase in AUC (1277.46 vs. 585.01 ng/ml · h), pro- longed t½ (27.87 ± 15.62 vs. 10.18 ± 6.5 h) and mean residence time (40.11 ± 25.72 vs. 17.42 ± 12.04 h) in comparison to pure Tmx. In addition, PLN exhibited significantly increased (P < 0.05) antitumor efficacy in DMBA-induced breast cancer model, when administered once in three days in comparison to Tmx daily dosing. This enhancement may be attributed to a probable reduction in Pgp efflux, decreased first-pass metabolism and lymphatic drug transport. Thus, Tmx-PLN exhibited enhanced potential to increase Tmx therapeutic efficacy in chronic treatment of breast cancer.

Modeling Huntington's disease: An insight on in-vitro and in-vivo models.

Huntington's disease is a neurodegenerative illness that causes neuronal death most extensively within the basal ganglia. There is a broad class of neurologic disorders associated with the expansion of polyglutamine (polyQ) repeats in numerous proteins. Several other molecular mechanisms have also been implicated in HD pathology, including brain-derived neurotrophic factor (BDNF), mitochondrial dysfunction, and altered synaptic plasticity in central spiny neurons. HD pathogenesis and the effectiveness of therapy approaches have been better understood through the use of animal models. The pathological manifestations of the disease were reproduced by early models of glutamate analog toxicity and mitochondrial respiration inhibition. Because the treatments available for HD are quite limited, it is important to have a definite preclinical model that mimics all the aspects of the disease. It can be used to study mechanisms and validate candidate therapies. Although there hasn't been much success in translating animal research into clinical practice, each model has something special to offer in the quest for a deeper comprehension of HD's neurobehavioral foundations. This review provides insight into various in-vitro-and in-vivo models of HD which may be useful in the screening of newer therapeutics for this incapacitating disorder.

Medicinal herbal remedies in neurodegenerative diseases: an update on antioxidant potential.

It has been widely documented that medicinal herbal remedies are effective, have fewer side effects than conventional medicine, and have a synergistic effect on health collaborations in the fight against complicated diseases. Traditional treatments for neurological problems in ancient times sometimes involved the use of herbal remedies and conventional methods from East Asian countries including India, Japan, China, and Korea. We collected and reviewed studies on plant-derived neuroprotective drugs and tested them in neurotoxic models. Basic research, preclinical and clinical transgene research can benefit from in silico, in vitro, and in vivo investigations. Research, summaries of the extracts, fractions, and herbal ingredients were compiled from popular scientific databases, which were then examined according to origin and bioactivity. Given the complex and varied causes of neurodegeneration, it may be beneficial to focus on multiple mechanisms of action and a neuroprotection approach. This approach aims to prevent cell death and restore function to damaged neurons, offering promising strategies for preventing and treating neurodegenerative diseases. Neurodegenerative illnesses can potentially be treated with natural compounds that have been identified as neuroprotective agents. To gain deeper insights into the neuropharmacological mechanisms underlying the neuroprotective and therapeutic properties of naturally occurring antioxidant phytochemical compounds in diverse neurodegenerative diseases, this study aims to comprehensively review such compounds, focusing on their modulation of apoptotic markers such as caspase, Bax, Bcl-2, and proinflammatory markers. In addition, we delve into a range of efficacies of antioxidant phytochemical compounds as neuroprotective agents in animal models. They reduce the oxidative stress of the brain and have been shown to have anti-apoptotic effects. Many researches have demonstrated that plant extracts or bioactive compounds can fight neurodegenerative disorders. Herbal medications may offer neurodegenerative disease patients' new treatments. This may be a cheaper and more culturally appropriate alternative to standard drugs for millions of people with age-related NDDs.