Harnessing Bioprinting Technologies for Diabetic Wound Regeneration.

A chronic metabolic condition, diabetes mellitus (DM), is becoming more common all over the globe. Diabetic complications include diabetic foot ulcers (DFUs). Between fifteen and twenty-five percent of people with diabetes will experience DFU at some point in their lives. Prolonged hospital stays and amputations are common outcomes of DFUs due to the absence of targeted therapy and appropriate wound dressings. Specialized DFU wound care is expected to be in high demand due to the anticipated increase in the prevalence of DM. Therefore, there is a strong need to enhance and create more effective wound dressings and therapies that are unique to DFU. Bioengineered tissues, individualised prostheses, and implants are just a few examples of how 3D bioprinting has revolutionised healthcare in the past decade. This review delves into the difficulties of wound management and explores how 3D bioprinting could improve existing treatment approaches and biomanufacturing composite 3D human skin substitutes as an alternative to skin grafting. To alleviate the healthcare burden caused by the rising incidence of DM, it will be crucial to co-develop 3D bioprinting technologies with new therapeutic techniques to address the unique pathophysiological problems of DFU in the future.

Lipid-Based Nanomedicine for Alzheimer's Disease: A Comprehensive Review of Recent Advances.

BACKGROUND: Alzheimer's disease (AD) is the most common form of dementia and is expected to greatly rise in future, making it a major worldwide health concern with severe impacts on individuals and society. Despite advancements in understanding the cellular and molecular aspects of Alzheimer's disease (AD) in recent decades, it still poses a significant problem. A major problem is accurately delivering drugs to diseased neurons while minimising effects on healthy neurons. This difficulty is worsened by the low water solubility of anti-Alzheimer's disease medicines and the blood-brain barrier (BBB) that hinders the entry of central nervous system pharmaceuticals that are highly lipophilic. OBJECTIVE: The focus of this article is on nanocarriers that are lipid-based. This is one of the more widely accepted methods of treating Alzheimer's disease, as it increases therapeutic efficacy while decreasing side effects related to cooperated neurological disorder payload. METHOD: Searched many databases for papers published under the title (including PubMed, Elsevier, and Google Scholar). RESULTS/CONCLUSION: Nano Lipid Carriers (NLCs) are recognized for their ability to target the brain effectively due to their lipid-loving properties and compatibility with living tissues. They improve the absorption of drugs in the brain while decreasing the accumulation of drugs in unintended organs. This work emphasises the importance of nano lipid carriers, which are lipophilic and biocompatible and have demonstrated exceptional targeting efficiency, making them an ideal carrier system for delivering medications to the brain.

Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin.

Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases.

Unravelling the Microbiome's Role in Healing Diabetic Wounds.

The process of wound healing is intricate and requires close coordination; any disruption to this process can have catastrophic results. It is hypothesized that chronic wounds that do not heal or that cease healing entirely can be caused by a combination of host factors and bacteria that are present in a wound bed or wound bed environment. There is currently a lack of understanding regarding the role that the cutaneous microbiome plays in the healing process of wounds, despite the fact that methods that do not rely on culture have revealed the role that the gut microbiome plays in human health and illness. In order to keep the host immune system in check, protect the epithelial barrier function, and ward off harmful microbes, skin commensals play a crucial role. This review compiles the research on the effects of microbiome modifications on wound healing and tissue regeneration from both clinical and pre-clinical investigations on a variety of chronic skin wounds. It is now clear that human skin commensals, symbionts, and pathogens all play a part in the inflammatory response, which in turn suggests a number of ways to treat wounds that are infected and not healing. To fully understand the function of the human skin microbiome in both short-term and long-term wound healing, additional study is required to reconcile the conflicting and contentious results of previous investigations.

Biobased Nanomaterials: Pioneering Innovations for Biomedical Advancements.

The purpose of this review article is to provide a complete overview of the fastdeveloping topic of biobased nanomaterials and the various uses that they have. An extensive study into the utilization of biological resources for nanotechnology has been motivated by the growing demand for materials that are both sustainable and favorable to the environment. In this review, the different uses of biobased nanomaterials across a variety of fields are investigated. When it comes to drug delivery systems, biosensors, nanocarriers, and catalysts, biobased nanomaterials are interesting choices because of their unique qualities. These properties include biocompatibility, programmable surface chemistry, and inherent functionality. Also, in the biomedical field, biobased nanomaterials offer promising prospects for revolutionizing medical diagnostics and therapies. Their biocompatibility, tunable surface chemistry, and inherent functionalities make them attractive candidates for applications such as targeted drug delivery, imaging contrast agents, and tissue engineering scaffolds. In addition, the study discusses the current difficulties and potential future developments in the industry, emphasizing the necessity of interdisciplinary collaboration and ongoing innovation. The incorporation of nanomaterials derived from biological sources into conventional applications holds tremendous potential for the advancement of sustainable development and provides solutions to global concerns. For the purpose of providing researchers, scientists, and professionals with a complete grasp of the synthesis, characterization, and applications of biobased nanomaterials, the purpose of this review is to serve as a helpful resource.

SEW2871 reduces seizures via the sphingosine 1-phosphate receptor-1 pathway in the pentylenetetrazol and phenobarbitone kindling model of drug-refractory epilepsy.

Epilepsy is a prevalent neurological disorder characterized by neuronal hypersynchronous discharge in the brain, leading to central nervous system (CNS) dysfunction. Despite the availability of anti-epileptic drugs (AEDs), resistance to AEDs is the greatest challenge in treating epilepsy. The role of sphingosine-1-phosphate-receptor 1 (S1PR1) in drug-resistant epilepsy is unexplored. This study investigated the effects of SEW2871, a potent S1PR1 agonist, on a phenobarbitone (PHB)-resistant pentylenetetrazol (PTZ)-kindled Wistar rat model. We measured the messenger ribonucleic acid (mRNA) expression of multi-drug resistance 1 (MDR1) and multi-drug resistance protein 5 (MRP5) as indicators for drug resistance. Rats received PHB + PTZ for 62 days to develop a drug-resistant epilepsy model. From day 48, SEW2871 (0.25, 0.5, 0.75 mg/kg, intraperitoneally [i.p.]) was administered for 14 days. Seizure scoring, behaviour, oxidative markers like reduced glutathione, catalase, superoxide dismutase, inflammatory markers like interleukin 1 beta tumour necrosis factor alpha, interferon gamma and mRNA expression (MDR1 and MRP5) were assessed, and histopathological assessments were conducted. SEW2871 demonstrated dose-dependent improvements in seizure scoring and neurobehavioral parameters with a reduction in oxidative and inflammation-induced neuronal damage. The S1PR1 agonist also downregulated MDR1 and MRP5 gene expression and significantly decreased the number of dark-stained pyknotic nuclei and increased cell density with neuronal rearrangement in the rat brain hippocampus. These findings suggest that SEW2871 might ameliorate epileptic symptoms by modulating drug resistance through downregulation of MDR1 and MRP5 gene expression.

Study of fingolimod, nitric oxide inhibitor, and P-glycoprotein inhibitor in modulating the P-glycoprotein expression via an endothelin-sphingolipid pathway in an animal model of pharmacoresistant epilepsy.

BACKGROUND: The overexpression of P-glycoprotein (P-gp) contributes to drug resistance in patients with epilepsy, and the change of P-gp expression located at the blood-brain barrier alienates the anti-seizure effects of P-gp substrates. Thus, the present study explored the effect of fingolimod (FTY720) acting through an endothelin-sphingolipid pathway on P-gp-induced pentylenetetrazol (PTZ)-kindled phenobarbital (PB)-resistant rats. MATERIALS AND METHODS: PTZ kindling (30 mg/kg; i.p.) and PB (40 mg/kg; orally) were used to develop an animal model of refractory epilepsy. The effect of Fingolimod on seizure score (Racine scale), plasma and brain levels of PB (high-performance liquid chromatography), and blood-brain barrier permeability (Evans blue dye) was determined. Further, Fingolimod's neuroprotective effect was determined by measuring the levels of various inflammatory cytokines, oxidative stress parameters, and neurotrophic factors in rat brain homogenate. The Fingolimod's effect on P-gp expression was estimated by reverse transcriptase-polymerase chain reaction and immunohistochemistry in rat brain. The H and E staining was done to determine the neuronal injury. RESULTS: Fingolimod significantly (P < 0.001) reduced the seizure score in a dose-dependent manner and alleviated the blood-brain barrier permeability. It decreased the P-gp expression, which further increased the brain PB concentration. Fingolimod significantly (P < 0.01) reduced oxidative stress as well as inflammation. Moreover, it attenuated the raised neuronal injury score in a resistant model of epilepsy. CONCLUSION: The modulation of the P-gp expression by Fingolimod improved drug delivery to the brain in an animal model of refractory epilepsy. Therefore, S1P signaling could serve as an additional therapeutic target to overcome refractoriness.

Artificial Intelligence in The Management of Neurodegenerative Disorders.

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality of life for people who suffer from them. The development of effective new methods for managing and treating neurodegenerative illnesses has been made possible by recent developments in computer technology. In this overview, we take a look at the prospects for applying computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative diseases. To review the current state of the field, this article discusses the potential of computational methods for early disease detection, quantifying disease progression, and understanding the underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated with these approaches and potential future directions. Moreover, it delves into the creation of computational models for the individualization of care for neurodegenerative diseases. The article concludes with suggestions for future studies and clinical applications, highlighting the advantages and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.

Hydrogel-based Drug Delivery System in Diabetes Management.

BACKGROUND: It is estimated that there are over 200 million people living with diabetes mellitus (DM) all over the world. It is a metabolic condition caused by decreased insulin action or secretion. Diabetes Mellitus is also known as Type 2 Diabetes Mellitus. Type 1 diabetes mellitus and type 2 diabetes mellitus are the two most common types of DM. Treatment for type 1 diabetes often consists of insulin replacement therapy, while treatment for type 2 diabetes typically consists of oral hypoglycemics. OBJECTIVE: Conventional dosing schedules for the vast majority of these medications come with a number of drawbacks, the most common of which are frequent dosing, a short half-life, and low bioavailability. Thus, innovative and regulated oral hypoglycemic medication delivery methods have been developed to reduce the limitations of standard dose forms. METHODS: The studies and reviews published under the title were looked up in several databases (including PubMed, Elsevier, and Google Scholar). RESULTS: Hydrogels made from biopolymers are three-dimensional polymeric networks that can be physically or chemically crosslinked. These networks are based on natural polymers and have an inherent hydrophilic quality because of the functional groups they contain. They have a very high affinity for biological fluids in addition to a high water content, softness, flexibility, permeability, and biocompatibility. The fact that these features are similar to those of a wide variety of soft living tissues paves the way for several potentials in the field of biomedicine. In this sense, hydrogels offer excellent platforms for the transport of medications and the controlled release of those drugs. Additionally, biopolymer-based hydrogels can be put as coatings on medical implants in order to improve the biocompatibility of the implants and to prevent medical diseases. CONCLUSION: The current review focuses on the most recent advancements made in the field of using biopolymeric hydrogels that are physically and chemically crosslinked, in addition to hydrogel coatings, for the purpose of providing sustained drug release of oral hypoglycemics and avoiding problems that are associated with the traditional dosage forms of oral hypoglycemics.

A Review on Natural Antioxidants for Their Role in the Treatment of Parkinson's Disease.

The neurodegenerative condition known as Parkinson's disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson's disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient's quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.

"Heart strings and purse strings" revisited: A preregistered replication and extension.

The Appraisal-Tendency Framework outlines that discrete emotions of similar valence behave differently, based on each emotion's specific appraisal profile. In the domain of pricing decisions, a seminal paper by Lerner and colleagues report incidental, negative emotions of disgust and sadness to show a divergent effect on spending decisions based on the perceived ownership of a commodity. Specifically, disgust-reduced spending while sadness increased spending on a new product. However, these researchers theorized, but did not statistically test the effects of emotion-induced motivational goals for sadness ("change circumstances") and disgust ("expel and avoid") as the drivers behind their divergent effects on spending. This study (N = 403) sought to replicate these primary findings in close adherence to the original protocol with better measurement properties in a different geographical location. It further extended the examination by empirically testing the distinct mediating processes for sadness and disgust by utilizing measures identified from a pilot study (N = 169) based on the original protocol. We found support for the effect of sadness (vs. disgust and neutral) in inducing higher choice prices through the motivational goal of changing circumstances, but the expected pattern of results for disgust was not replicated. Additionally, we examined the role of arousal in this context as a factor driving the effect of these emotions on spending. Our research offers new insights regarding the well-known "misery-is not miserly" effect for practitioners while also providing impetus for future research on the endowment effect. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pentylenetetrazole Induced Kindling Model of Refractory Epilepsy: A Proof-of-concept Study to Explore Dose and Time Range of Phenobarbital in Rats.

Introduction: Drug-resistant epilepsy is an unmet medical condition that impacts 30% of epileptic patients. Numerous antiseizure drugs have already been developed but they provide only symptomatic relief and do not target the underlying pathogenesis. Preclinical models provide opportunities to gain insights into obscure mechanisms of drug-resistant epilepsy. Current animal models possess lacunae that need rectification and validation to discover novel antiepileptic drugs. The present study aims to validate 3 different doses of phenobarbital at 2 different periods. Methods: Pentylenetetrazole was given at a sub-convulsive dose (30 mg/kg/day/intraperitoneal [IP]) for 28 days to develop kindling in male Wistar rats. Further, kindled rats were divided into the following four groups: Pentylenetetrazole control, pentylenetetrazole and phenobarbital (20 mg/kg), pentylenetetrazole and phenobarbital 40 mg/kg, and pentylenetetrazole and phenobarbital (60 mg/kg). They were assessed on days 14 and 28 post-kindling. Seizure scoring, oxidative stress, phenobarbital plasma levels, and histopathology of hippocampal neurons were analyzed. Results: The results showed that the combination of pentylenetetrazole and phenobarbital (40 and 60 mg/kg) remarkably decreased seizure score, elucidated higher antioxidant effect, and prevented neuronal injury on day 14, whereas increased seizure score, oxidative stress, and neuronal death was observed with chronic administration of pentylenetetrazole and phenobarbital in kindled rats at day 28. Moreover, phenobarbital levels in blood were significantly increased at day 28 of phenobarbital treatment compared to day 14. Conclusion: The adapted protocol with phenobarbital 40 mg/kg dose could be of great potential in screening antiseizure drugs in refractory epilepsy.

The curious case of threat-awe: A theoretical and empirical reconceptualization.

Threat-based awe, or threat-awe, has been conceptualized as a fear-centric, negative-valenced variant of awe, although awe is a positive emotion embodying wonder and amazement. This research, however, argues that threat-awe is a mixed emotion rather than a negatively valenced subaspect of awe. We tested this conceptualization using two methodologies: (a) the theoretical framework of cognitive appraisals and (b) measures of ambivalence (an emotion co-occurrence index of bivalence, the Evaluative Space Grid, and a four-item scale to measure mixed emotions). Five studies (N = 1,140) compared threat-awe's appraisal profile and valence perceptions to univalenced, positive (awe, pride, happiness) and negative (fear) emotions. Research suggests that appraisal profiles of mixed emotions are close to their component emotions but distinct on certain appraisal dimensions. The empirical measures of valence demonstrate that threat-awe is felt as awe and fear in concert. Further, in terms of appraisals, threat-awe's appraisal profile is distinct from awe and fear on the dimensions of vastness, pleasantness, and situational control. Together, the two approaches-cognitive appraisals and measures of valence-provide convergent evidence that threat-awe is a mixed emotion. In conceptually clarifying threat-awe, we contribute to the nascent literature on mixed emotions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Role of protein tyrosine phosphatase 1B inhibitor in central insulin resistance and associated cognitive deficits.

BACKGROUND: Protein tyrosine phosphatase 1B (PTP1B) inhibitors are potential candidates for the treatment of peripheral insulin resistance and diabetes mellitus. Similar to peripheral action within the brain also, PTP1B activation impairs insulin signaling pathways. Activation of PTP1B in brain also accentuates neuroinflammation, oxidative stress and decreases neurotrophic factors in various brain dysfunctions including cognitive decline. OBJECTIVES: The main objective of our study was to elucidate the role of alendronate, a potent PTP1B inhibitor (blood brain barrier crossing bisphosphonate) in central insulin resistance and associated memory deficits. METHODOLOGY: To induce central insulin resistance, streptozotocin (3 mg/kg) intracerebroventricular (ICV) was administered in two alternate days (1st and 3rd). After 21 days, memory was assessed via using the passive avoidance and Morris water maze paradigm. At the end of behavioral studies, animals were sacrificed to assess a variety of biochemical and molecular parameters in the hippocampus and cerebral cortex region of the brain. Treatment drug alendronate (3 mg/kg/day, p.o) and standard drug donepezil (3 mg/kg/i.p.) were administered from the 3rd day of STZ administration till the end of the study. Inhibition of PTP1B activates phosphoinsotide-3 kinase (PI3 K) (down-stream regulator of insulin signaling pathway).Thus, to illuminate the mechanism of action of alendronate, PI3 K inhibitor, wortmannin was administered in presence of alendronate in one group. RESULTS: Administration of alendronate to ICV streprozotocin treated rats resulted in modulation of the insulin signaling pathway and associated behavioral, biochemical and molecular changes in central insulin resistance. However, the protective effect of alendronate was entirely vanished when it was administered in the presence of wortmannin. CONCLUSION: Alendronate can be an important treatment strategy in central insulin signaling pathway dysfunction and associated cognitive deficits. Protective effect of alendronate is via modulation of PI3-K/Akt signaling pathway.

A novel approach of targeting refractory epilepsy: Need of an hour.

The refractory epilepsy adds to the global burden of epilepsy as about 25 % of all patients with epilepsy present drug-resistant epilepsy. The P-glycoprotein (P-gp) plays a vital role in the mechanism of resistance in epilepsy. The AED levels in the brain are regulated by the P-gp transport. The upregulation of P-gp results in low concentration of AEDs inside the brain parenchyma and thus leads to resistance. There are three main conditions which lead to decrease transport of AEDs in refractory epilepsy. First being AEDs as substrate of P-gp; secondly, the elevated expression of P-gp in patients with drug resistant epilepsy as compared to drug-responsive patients; thirdly, the low brain AED concentration in refractory epilepsy in comparison to drug-responsive epilepsy. Therefore, determination of P-gp substrate should be a criterion for the selection of new AED for management of refractory epilepsy. This review highlights various tools which help in identification of P-gp substrates and also illustrates a concept of using various novel non-P-gp substrates which can cross the blood brain barrier and leads to enhanced accumulation inside the brain. Hence, these non P-gp substrates can be used as an add on treatment for the management of resistant epilepsy.

The misery-is-not-miserly effect revisited: Replication despite opportunities for compensatory consumption.

Sadness increases how much decision makers pay to acquire goods, even when decision makers are unaware of it. This effect is coined the "misery-is-not-miserly effect". The paper that first established this effect is the second most-cited article appearing in Psychological Science in 2004. In light of its impact, the present study sought to assess whether the misery-is-not-miserly effect would replicate (a) in a novel context and (b) even when another way of alleviating a sense of loss (i.e., compensatory consumption) was available. Results revealed that the effect replicated in the novel context and, despite a prediction otherwise, even when individuals had an opportunity to engage in compensatory consumption. Moreover, a meta-analysis of the original effect and that observed in the present study yielded a small-to-medium effect (Cohen's d = 0.43). As such, the present study lends evidentiary support to the misery-is-not-miserly effect and provides impetus for future research exploring the impact of sadness on consumer decision-making, specifically, and of emotion on decision processes, more generally.

Cracking novel shared targets between epilepsy and Alzheimer's disease: need of the hour.

Epilepsy and Alzheimer's disease (AD) are interconnected. It is well known that seizures are linked with cognitive impairment, and there are various shared etiologies between epilepsy and AD. The connection between hyperexcitability of neurons and cognitive dysfunction in the progression of AD or epileptogenesis plays a vital role for improving selection of treatment for both diseases. Traditionally, seizures occur less frequently and in later stages of age in patients with AD which in turn implies that neurodegeneration causes seizures. The role of seizures in early stages of pathogenesis of AD is still an issue to be resolved. So, it is well timed to analyze the common pathways involved in pathophysiology of AD and epilepsy. The present review focuses on similar potential underlying mechanisms which may be related to the causes of seizures in epilepsy and cognitive impairment in AD. The proposed review will focus on many possible newer targets like abnormal expression of various enzymes like GSK-3ß, PP2A, PKC, tau hyperphosphorylation, MMPs, caspases, neuroinflammation and oxidative stress associated with number of neurodegenerative diseases linked with epilepsy. The brief about the prospective line of treatment of both diseases will also be discussed in the present review.

Geographically varying effects of weather on tobacco consumption: implications for health marketing initiatives.

Weather and its fluctuations have been found to influence the consumption of negative hedonic goods. However, such findings are of limited use to health marketers who cannot control the weather, and hence, its effects. The current research utilizes data obtained at the zip-code level to study geographical variations in the effect of weather on tobacco consumption across the entire continental United States. The results allow health marketers to identify areas that will be most responsive to marketing efforts aimed at curtailing negative hedonic consumption and thus implement more effective, region-specific initiatives.