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Dengue fever is currently a major global issue, especially in tropical and subtropical countries. The absence of specific antiviral medications supports alternative dengue treatment strategies. South Asian countries have been using Carica papaya leaves as a traditional remedy for dengue for many years. Carica papaya possesses several biological features, including anti-inflammatory, antiviral, cancer-fighting, anti-diabetic, and antioxidant qualities. Additionally, numerous studies have demonstrated that bioactive compounds found in papaya leaf extracts, including carpaine, dehydrocarpaine I and II, chymopapain, and papain, significantly influence platelet counts, while phenolic compounds, such as chlorogenic acid, kaemferol, protocatechuic acid, quercetin, and 5,7-dimethoxycoumarin significantly inhibit viral replication in dengue patients, with negligible side effects. Carica papaya may be considered a viable pharmacological candidate with several targets for treating dengue. It has been shown to prevent infections, reduce oxidative stress, control cytokine storms and the immune system, lessen thrombocytopenia, and increase the body's protein and hemoglobin levels. This literature review highlights the pathophysiological mechanism of dengue, as well as the pharmacological action of Carica papaya, both of which combat this debilitating disease. Despite these findings, additional investigation, including clinical studies, is necessary to confirm the effectiveness and safety of papaya-based treatments. It is necessary to address issues like standardizing papaya extracts, figuring out the best dosages, and assessing any drug interactions. [ABSTRACT FROM AUTHOR]

The glass transition temperature of polymers is a key parameter in meeting the application requirements for energy absorption. Previous studies have provided some data from slow, expensive trial-and-error procedures. By recognizing these data, machine learning algorithms are able to extract valuable knowledge and disclose essential insights. In this study, a dataset of 7174 samples was utilized. The polymers were numerically represented using two methods: Morgan fingerprint and molecular descriptor. During preprocessing, the dataset was scaled using a standard scaler technique. We removed the features with small variance from the dataset and used the Pearson correlation technique to exclude the features that were highly connected. Then, the most significant features were selected using the recursive feature elimination method. Nine machine learning techniques were employed to predict the glass transition temperature and tune their hyperparameters. The models were compared using the performance metrics of mean absolute error (MAE), root mean square error (RMSE), and coefficient of determination (R2). We observed that the extra tree regressor provided the best results. Significant features were also identified using statistical machine learning methods. The SHAP method was also employed to demonstrate the influence of each feature on the model's output. This framework can be adaptable to other properties at a low computational expense. [ABSTRACT FROM AUTHOR]

Cucumber plants commonly suffer from Fusarium wilt disease, which is caused by Fusarium oxysporum f. sp. cucumerinum (Foc). Although resistant cultivars assist with Fusarium wilt disease control, enhancement of the virulence of Foc has been identified after monoculture of wilt-resistant cultivars. To investigate the biological characteristics that contribute to the virulence evolution of Foc, a wildtype strain foc-3b (WT) and its virulence-enhanced variant Ra-4 (InVir) were compared in terms of their growth, reproduction, stress tolerance, and colonization in cucumber plants. The InVir strain showed similar culture characteristics on PDA media to the WT strain but produced significantly more conidia (>two fold), with a distinctly higher germination rate (>four fold) than the WT strain. The colony diameter of the InVir strain increased faster than the WT strain on PDA plates; however, the mycelia dry weight of the InVir was significantly lower (<70%) than that of the WT harvested from PDB. The InVir strain exhibited a significant increase in tolerance to osmolality (1 M NaCl, 1 M KCl, etc.). The GFP-labeled InVir strain propagated in the cucumber vascular faster than the WT strain. These results suggest that increased conidia production and germination in vitro may correlate with virulence enhancement in Fusarium oxysporum f. sp. cucumerinum. This study will provide an insight into its virulence evolution and help us understand the mechanisms underlying the evolutionary biology of F. oxysporum. [ABSTRACT FROM AUTHOR]

Diabetes is a chronic disease caused by a persistently high blood sugar level, causing other chronic diseases, including cardiovascular, kidney, eye, and nerve damage. Prompt detection plays a vital role in reducing the risk and severity associated with diabetes, and identifying key risk factors can help individuals become more mindful of their lifestyles. In this study, we conducted a questionnaire-based survey utilizing standard diabetes risk variables to examine the prevalence of diabetes in Bangladesh. To enable prompt detection of diabetes, we compared different machine learning techniques and proposed an ensemble-based machine learning framework that incorporated algorithms such as decision tree, random forest, and extreme gradient boost algorithms. In order to address class imbalance within the dataset, we initially applied the synthetic minority oversampling technique (SMOTE) and random oversampling (ROS) techniques. We evaluated the performance of various classifiers, including decision tree (DT), logistic regression (LR), support vector machine (SVM), gradient boost (GB), extreme gradient boost (XGBoost), random forest (RF), and ensemble technique (ET), on our diabetes datasets. Our experimental results showed that the ET outperformed other classifiers; to further enhance its effectiveness, we fine-tuned and evaluated the hyperparameters of the ET. Using statistical and machine learning techniques, we also ranked features and identified that age, extreme thirst, and diabetes in the family are significant features that prove instrumental in the detection of diabetes patients. This method has great potential for clinicians to effectively identify individuals at risk of diabetes, facilitating timely intervention and care. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is a neurological impairment condition that severely impairs cognitive, linguistic, object recognition, interpersonal, and communication skills. Its main cause is genetic, and early treatment and identification can reduce the patient's expensive medical costs and lengthy examinations. We developed a machine learning (ML) architecture that is capable of effectively analysing autistic children's datasets and accurately classifying and identifying ASD traits. We considered the ASD screening dataset of toddlers in this study. We utilised the SMOTE method to balance the dataset, followed by feature transformation and selection methods. Then, we utilised several classification techniques in conjunction with a hyperparameter optimisation approach. The AdaBoost method yielded the best results among the classifiers. We employed ML and statistical approaches to identify the most crucial characteristics for the rapid recognition of ASD patients. We believe our proposed framework could be useful for early diagnosis and helpful for clinicians. [ABSTRACT FROM AUTHOR]

Physical activity among people of all ages has been decreasing at an alarming rate in recent years. Active commuting is recognized as a public health strategy to increase physical activity. The objectives of the study were to determine the habit of active commuting and the associated factors of commute mode choice among university students in the secondary city of Sylhet, Bangladesh. The study was cross-sectional in nature, and information from three hundred and forty-eight students was collected through an online survey using Google Forms. In addition to basic statistical tools, a multiple logistic regression model was applied to identify the factors that were associated with the commuting mode choice of the students. The results have shown that the prevalence of using an active commuting mode is not at a satisfactory level (43%). No remarkable difference in commuting behavior was found between males and females. The "distance between campus and students' residences" and the "mode of commuting preferred by roommate or classmate" are the most significant factors influencing students' commuting choices and related actions. In addition, respondents with lower socio-economic conditions have more of a tendency to use active modes of commuting. Weather, time constraints, road safety, and family residence in rural or urban areas all have an impact on choosing an active mode of transportation for attending classes, but none is overly significant. It is recommended to promote the health and financial benefits of active commuting. Necessary facilities should be constructed to increase the level of active commuting, such as additional residential halls near campus and developing a built environment on the campus for walking and cycling for both male and female students. [ABSTRACT FROM AUTHOR]

Biofilm is a complex matrix made up of extracellular polysaccharides, DNA, and proteins that protect bacteria against physical, chemical, and biological stresses and allow them to survive in harsh environments. Safe and healthy foods are mandatory for saving lives. However, foods can be contaminated by pathogenic microorganisms at any stage from farm to fork. The contaminated foods allow pathogenic microorganisms to form biofilms and convert the foods into stigmatized poison for consumers. Biofilm formation by pathogenic microorganisms in agri-farm industries is still poorly understood and intricate to control. In biofilms, pathogenic bacteria are dwelling in a complex manner and share their genetic and physicochemical properties making them resistant to common antimicrobial agents. Therefore, finding the appropriate antibiofilm approaches is necessary to inhibit and eradicate the mature biofilms from foods and food processing surfaces. Advanced studies have already established several emerging antibiofilm approaches including plant- and microbe-derived biological agents, and they proved their efficacy against a broad-spectrum of foodborne pathogens. This review investigates the pathogenic biofilm-associated problems in agri-farm industries, potential remedies, and finding the solution to overcome the current challenges of antibiofilm approaches. [ABSTRACT FROM AUTHOR]

The left figure illustrates a 3D complex protein-ligand interaction, while the right figure represents a 2D complex protein-ligand interaction. When the protein -ligand complex is first aligned on the reference protein backbone and then the RMSD of the ligand heavy atoms is measured, the RMSD of the ligand is presented in the plot. Keywords: kidney fibrosis; chronic kidney disease; TGF R-1; flavonoids; pharmacokinetics; molecular docking; molecular dynamics simulations EN kidney fibrosis chronic kidney disease TGF R-1 flavonoids pharmacokinetics molecular docking molecular dynamics simulations 1764 19 11/17/22 20221101 NES 221101 1. An In-Silico Identification of Potential Flavonoids against Kidney Fibrosis Targeting TGF R-1. [Extracted from the article]

Dendritic cells (DCs) are specialized antigen-presenting cells in humans and animals that provide antigen-specific T-cell immunity in the body. It also establishes a linkage between innate and adaptive immune responses. Various studies have shown that malignancies or cancer may impair DCs and effector T-cell functions. DCs have now become a new molecular target for the treatment of cancer. Modified matured DCs could be novel biological modifiers to treat various diseases, including cancer. This review aims to provide an update on the impacts of various plant materials and their phytochemicals on DC-based cancer immunotherapy. Existing literature on DC-based cancer immunotherapy and plant-based pharmacological modulators has been explored over the last decade using various online databases such as Google Scholar, PubMed, Science Direct, and Scopus. Mounting evidence from preclinical and clinical findings suggests that various plants and their bioactive phytochemicals are effective in modulating the immune system and signaling pathways involved in anti-tumor immunity. Despite the prospective role of herbs in DC-based cancer immunotherapy, most of the studies are limited by either preclinical models or crude plant extracts. This review provides a useful perspective for developing potential plant-derived pharmacological modulators in DC-based cancer immunotherapy. [ABSTRACT FROM AUTHOR]

One of the common types of cancer for women is ovarian cancer. Still, at present, there are no drug therapies that can properly cure this deadly disease. However, early-stage detection could boost the life expectancy of the patients. The main aim of this work is to apply machine learning models along with statistical methods to the clinical data obtained from 349 patient individuals to conduct predictive analytics for early diagnosis. In statistical analysis, Student's t-test as well as log fold changes of two groups are used to find the significant blood biomarkers. Furthermore, a set of machine learning models including Random Forest (RF), Support Vector Machine (SVM), Decision Tree (DT), Extreme Gradient Boosting Machine (XGBoost), Logistic Regression (LR), Gradient Boosting Machine (GBM) and Light Gradient Boosting Machine (LGBM) are used to build classification models to stratify benign-vs.-malignant ovarian cancer patients. Both of the analysis techniques recognized that the serumsamples carbohydrate antigen 125, carbohydrate antigen 19-9, carcinoembryonic antigen and human epididymis protein 4 are the top-most significant biomarkers as well as neutrophil ratio, thrombocytocrit, hematocrit blood samples, alanine aminotransferase, calcium, indirect bilirubin, uric acid, natriumas as general chemistry tests. Moreover, the results from predictive analysis suggest that the machine learning models can classify malignant patients from benign patients with accuracy as good as 91%. Since generally, early-stage detection is not available, machine learning detection could play a significant role in cancer diagnosis. [ABSTRACT FROM AUTHOR]

Clonostachys rosea is an important mycoparasite, with great potential for controlling numerous plant fungal diseases. Understanding the mechanisms and modes of action will assist the development and application of this biocontrol fungus. In this study, the highly efficient C. rosea 67-1 strain was marked with the green fluorescent protein (GFP), and the transformant possessed the same biological characteristics as the wild-type strain. Fungal interactions with Botrytis cinerea during co-culture and encounter on tomato leaves were assessed by fluorescence confocal and electron microscopy. The results indicated that once the two fungi met, the hyphae of C. rosea grew alongside those of B. cinerea, then attached tightly to the host and developed special structures, via which the biocontrol fungus penetrated the host and absorbed nutrients, eventually disintegrating the cells of the pathogen. Mycoparasitism to B. cinerea was also observed on tomato leaves, suggesting that C. rosea can colonize on plants and act following the invasion of the pathogenic fungus. [ABSTRACT FROM AUTHOR]

Neuropilin-1 (NRP1) is a recently identified glycoprotein that is an important host factor for SARS-CoV-2 infection. On the other hand, angiotensin-converting enzyme-2 (ACE2) acts as a receptor for SARS-CoV-2. Additionally, both NRP1 and ACE2 express in the kidney and are associated with various renal diseases, including renal carcinoma. Therefore, the expression profiles of NRP1 and ACE2 in kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP) patients from the various cancer databases were investigated along with their impact on patients' survivability. In addition, coexpression analysis of genes involved in COVID-19, KIRC, and KIRP concerning NRP1 and ACE2 was performed. The results demonstrated that both t NRP1 and ACE2 expressions are upregulated in KIRC and KIRP compared to healthy conditions and are significantly correlated with the survivability rate of KIRC patients. A total of 128 COVID-19-associated genes are coexpressed, which are positively associated with NRP1 and ACE2 both in KIRC and KIRP. Therefore, it might be suggested that, along with the ACE2, high expression of the newly identified host factor NRP1 in renal carcinomas may play a vital role in the increased risk of SARS-CoV-2 infection and survivability of COVID-19 patients suffering from kidney cancers. The findings of this investigation will be helpful for further molecular studies and prevention and/or treatment strategies for COVID-19 patients associated with renal carcinomas. [ABSTRACT FROM AUTHOR]

CCNs are a specific type of matricellular protein, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members, which exist only in vertebrates. The architecture of CCN proteins is multi-modular comprising four distinct modules. CCN Proteins achieve their primary functional activities by binding with several integrin7 receptors. The CCN family has been linked to cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, chondrogenesis, and wound healing, among other biological interactions. Breast cancer is the most commonly diagnosed cancer worldwide and CCN regulated breast cancer stands at the top. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. The pro-tumorigenic CCN1, CCN2, CCN3, and CCN4 may lead to human breast cancer, although the anti-tumorigenic actions of CCN5 and CCN6 are also present. Several studies have been conducted on CCN proteins and cancer in recent years. CCN1 and CCN3 have been shown to exhibit a dual nature of tumor inhibition and tumor suppression to some extent in quiet recent time. Pharmacological advances in treating breast cancer by targeting CCN proteins are also reported. In our study, we intend to provide an overview of these research works while keeping breast cancer in focus. This information may facilitate early diagnosis, early prognosis and the development of new therapeutic strategies. [ABSTRACT FROM AUTHOR]

Ducks are the natural reservoir of influenza A virus and the central host for the avian influenza virus (AIV) subtype H5N1, which is highly pathogenic. Semi-scavenging domestic ducks allow for the reemergence of new influenza subtypes which could be transmitted to humans. We collected 844 cloacal swabs from semi-scavenging ducks inhabiting seven migratory bird sanctuaries of Bangladesh for the molecular detection of avian influenza genes. We detected the matrix gene (M gene) using real-time RT–PCR (RT–qPCR). Subtyping of the AIV-positive samples was performed by RT–qPCR specific for H5, H7, and H9 genes. Out of 844 samples, 21 (2.488%) were positive for AIV. Subtyping of AIV positive samples (n = 21) revealed that nine samples (42.85%) were positive for the H9 subtype, five (23.80%) were positive for H5, and seven (33.33%) were negative for the three genes (H5, H7, and H9). We detected the same genes after propagating the virus in embryonated chicken eggs from positive samples. Semi-scavenging ducks could act as carriers of pathogenic AIV, including the less pathogenic H9 subtype. This can enhance the pathogenicity of the virus in ducks by reassortment. The large dataset presented in our study from seven areas should trigger further studies on AIV prevalence and ecology. [ABSTRACT FROM AUTHOR]

Kidney diseases are regarded as one of the major public health issues in the world. The objectives of this study were: (i) to investigate the causative factors involved in kidney disease and the therapeutic aspects of Moringa oleifera, as well as (ii) the effectiveness of M. oleifera in the anti-inflammation and antioxidant processes of the kidney while minimizing all potential side effects. In addition, we proposed a hypothesis to improve M. oleifera based drug development. This study was updated by searching the key words M. oleifera on kidney diseases and M. oleifera on oxidative stress, inflammation, and fibrosis in online research databases such as PubMed and Google Scholar. The following validation checking and scrutiny analysis of the recently published articles were used to explore this study. The recent existing research has found that M. oleifera has a plethora of health benefits. Individual medicinal properties of M. oleifera leaf extract, seed powder, stem extract, and the whole extract (ethanol/methanol) can up-increase the activity of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), while decreasing the activity of inflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2. In our study, we have investigated the properties of this plant against kidney diseases based on existing knowledge with an updated review of literature. Considering the effectiveness of M. oleifera, this study would be useful for further research into the pharmacological potential and therapeutic insights of M. oleifera, as well as prospects of Moringa-based effective medicine development for human benefits. [ABSTRACT FROM AUTHOR]

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and a close association between acute kidney injury (AKI) and CKD has recently been identified. Black cumin (Nigella sativa) has been shown to be effective in treating various kidney diseases. Accumulating evidence shows that black cumin and its vital compound, thymoquinone (TQ), can protect against kidney injury caused by various xenobiotics, namely chemotherapeutic agents, heavy metals, pesticides, and other environmental chemicals. Black cumin can also protect the kidneys from ischemic shock. The mechanisms underlying the kidney protective potential of black cumin and TQ include antioxidation, anti-inflammation, anti-apoptosis, and antifibrosis which are manifested in their regulatory role in the antioxidant defense system, NF-κB signaling, caspase pathways, and TGF-β signaling. In clinical trials, black seed oil was shown to normalize blood and urine parameters and improve disease outcomes in advanced CKD patients. While black cumin and its products have shown promising kidney protective effects, information on nanoparticle-guided targeted delivery into kidney is still lacking. Moreover, the clinical evidence on this natural product is not sufficient to recommend it to CKD patients. This review provides insightful information on the pharmacological benefits of black cumin and TQ against kidney damage. [ABSTRACT FROM AUTHOR]

Aging is an unavoidable part of life. The more aged we become, the more susceptible we become to various complications and damages to the vital organs, including the kidneys. The existing drugs for kidney diseases are mostly of synthetic origins; thus, natural compounds with minimal side-effects have attracted growing interest from the scientific community and pharmaceutical companies. A literature search was carried out to collect published research information on the effects of resveratrol on kidney aging. Recently, resveratrol has emerged as a potential anti-aging agent. This versatile polyphenol exerts its anti-aging effects by intervening in various pathologies and multi-signaling systems, including sirtuin type 1, AMP-activated protein kinase, and nuclear factor-κB. Researchers are trying to figure out the detailed mechanisms and possible resveratrol-mediated interventions in divergent pathways at the molecular level. This review highlights (i) the causative factors implicated in kidney aging and the therapeutic aspects of resveratrol, and (ii) the effectiveness of resveratrol in delaying the aging process of the kidney while minimizing all possible side effects. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most prevailing neurodegenerative diseases, characterized by memory dysfunction and the presence of hyperphosphorylated tau and amyloid β (Aβ) aggregates in multiple brain regions, including the hippocampus and cortex. The exact etiology of AD has not yet been confirmed. However, epidemiological reports suggest that populations who were exposed to environmental hazards are more likely to develop AD than those who were not. Arsenic (As) is a naturally occurring environmental risk factor abundant in the Earth's crust, and human exposure to As predominantly occurs through drinking water. Convincing evidence suggests that As causes neurotoxicity and impairs memory and cognition, although the hypothesis and molecular mechanism of As-associated pathobiology in AD are not yet clear. However, exposure to As and its metabolites leads to various pathogenic events such as oxidative stress, inflammation, mitochondrial dysfunctions, ER stress, apoptosis, impaired protein homeostasis, and abnormal calcium signaling. Evidence has indicated that As exposure induces alterations that coincide with most of the biochemical, pathological, and clinical developments of AD. Here, we overview existing literature to gain insights into the plausible mechanisms that underlie As-induced neurotoxicity and the subsequent neurological deficits in AD. Prospective strategies for the prevention and management of arsenic exposure and neurotoxicity have also been discussed. [ABSTRACT FROM AUTHOR]

Simple Summary: Although biological information and the molecular classification of ependymoma have been studied, the treatment systems for ependymoma are still insufficient. In addition, because the disease occurs infrequently, it is difficult to obtain sufficient data to conduct large-scale or randomized clinical trials. Therefore, this study is intended to emphasize the importance of understanding its pathological characteristics and prognosis as well as developing treatments for ependymoma through multilateral studies. Glial cells comprise the non-sensory parts of the central nervous system as well as the peripheral nervous system. Glial cells, also known as neuroglia, constitute a significant portion of the mammalian nervous system and can be viewed simply as a matrix of neural cells. Despite being the "Nervenkitt" or "glue of the nerves", they aptly serve multiple roles, including neuron repair, myelin sheath formation, and cerebrospinal fluid circulation. Ependymal cells are one of four kinds of glial cells that exert distinct functions. Tumorigenesis of a glial cell is termed a glioma, and in the case of an ependymal cell, it is called an ependymoma. Among the various gliomas, an ependymoma in children is one of the more challenging brain tumors to cure. Children are afflicted more severely by ependymal tumors than adults. It has appeared from several surveys that ependymoma comprises approximately six to ten percent of all tumors in children. Presently, the surgical removal of the tumor is considered a standard treatment for ependymomas. It has been conspicuously evident that a combination of irradiation therapy and surgery is much more efficacious in treating ependymomas. The main purpose of this review is to present the importance of both a deep understanding and ongoing research into histopathological features and prognoses of ependymomas to ensure that effective diagnostic methods and treatments can be developed. [ABSTRACT FROM AUTHOR]

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex neuro-developmental disorder that affects social skills, language, speech and communication. Early detection of ASD individuals, especially children, could help to devise and strategize right therapeutic plan at right time. Human faces encode important markers that can be used to identify ASD by analyzing facial features, eye contact, and so on. In this work, an improved transfer-learning-based autism face recognition framework is proposed to identify kids with ASD in the early stages more precisely. Therefore, we have collected face images of children with ASD from the Kaggle data repository, and various machine learning and deep learning classifiers and other transfer-learning-based pre-trained models were applied. We observed that our improved MobileNet-V1 model demonstrates the best accuracy of 90.67% and the lowest 9.33% value of both fall-out and miss rate compared to the other classifiers and pre-trained models. Furthermore, this classifier is used to identify different ASD groups investigating only autism image data using k-means clustering technique. Thus, the improved MobileNet-V1 model showed the highest accuracy (92.10%) for k = 2 autism sub-types. We hope this model will be useful for physicians to detect autistic children more explicitly at the early stage. [ABSTRACT FROM AUTHOR]

Mounting evidence support the potential benefits of functional foods or nutraceuticals for human health and diseases. Black cumin (Nigella sativa L.), a highly valued nutraceutical herb with a wide array of health benefits, has attracted growing interest from health-conscious individuals, the scientific community, and pharmaceutical industries. The pleiotropic pharmacological effects of black cumin, and its main bioactive component thymoquinone (TQ), have been manifested by their ability to attenuate oxidative stress and inflammation, and to promote immunity, cell survival, and energy metabolism, which underlie diverse health benefits, including protection against metabolic, cardiovascular, digestive, hepatic, renal, respiratory, reproductive, and neurological disorders, cancer, and so on. Furthermore, black cumin acts as an antidote, mitigating various toxicities and drug-induced side effects. Despite significant advances in pharmacological benefits, this miracle herb and its active components are still far from their clinical application. This review begins with highlighting the research trends in black cumin and revisiting phytochemical profiles. Subsequently, pharmacological attributes and health benefits of black cumin and TQ are critically reviewed. We overview molecular pharmacology to gain insight into the underlying mechanism of health benefits. Issues related to pharmacokinetic herb–drug interactions, drug delivery, and safety are also addressed. Identifying knowledge gaps, our current effort will direct future research to advance potential applications of black cumin and TQ in health and diseases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative brain disorder characterized by a progressive decline in memory and cognition, mostly affecting the elderly. Numerous functional bioactives have been reported in marine organisms, and anti-Alzheimer's agents derived from marine resources have gained attention as a promising approach to treat AD pathogenesis. Marine sterols have been investigated for several health benefits, including anti-cancer, anti-obesity, anti-diabetes, anti-aging, and anti-Alzheimer's activities, owing to their anti-inflammatory and antioxidant properties. Marine sterols interact with various proteins and enzymes participating via diverse cellular systems such as apoptosis, the antioxidant defense system, immune response, and cholesterol homeostasis. Here, we briefly overview the potential of marine sterols against the pathology of AD and provide an insight into their pharmacological mechanisms. We also highlight technological advances that may lead to the potential application of marine sterols in the prevention and therapy of AD. [ABSTRACT FROM AUTHOR]

The global burden of chronic kidney disease (CKD) intertwined with cardiovascular disease has become a major health problem. Oxidative stress (OS) plays an important role in the pathophysiology of CKD. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant responsive element (ARE) antioxidant system plays a critical role in kidney protection by regulating antioxidants during OS. Heme oxygenase-1 (HO-1), one of the targets of Nrf2-ARE, plays an important role in regulating OS and is protective in a variety of human and animal models of kidney disease. Thus, activation of Nrf2-HO-1 signaling may offer a potential approach to the design of novel therapeutic agents for kidney diseases. In this review, we have discussed the association between OS and the pathogenesis of CKD. We propose Nrf2-HO-1 signaling-mediated cell survival systems be explored as pharmacological targets for the treatment of CKD and have reviewed the literature on the beneficial effects of small molecule natural products that may provide protection against CKD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a decline in cognitive function and neuronal damage. Although the precise pathobiology of AD remains elusive, accumulating evidence suggests that mitochondrial dysfunction is one of the underlying causes of AD. Mutations in mitochondrial or nuclear DNA that encode mitochondrial components may cause mitochondrial dysfunction. In particular, the dysfunction of electron transport chain complexes, along with the interactions of mitochondrial pathological proteins are associated with mitochondrial dysfunction in AD. Mitochondrial dysfunction causes an imbalance in the production of reactive oxygen species, leading to oxidative stress (OS) and vice versa. Neuroinflammation is another potential contributory factor that induces mitochondrial dysfunction. Phytochemicals or other natural compounds have the potential to scavenge oxygen free radicals and enhance cellular antioxidant defense systems, thereby protecting against OS-mediated cellular damage. Phytochemicals can also modulate other cellular processes, including autophagy and mitochondrial biogenesis. Therefore, pharmacological intervention via neuroprotective phytochemicals can be a potential strategy to combat mitochondrial dysfunction as well as AD. This review focuses on the role of phytochemicals in mitigating mitochondrial dysfunction in the pathogenesis of AD. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI), a critical syndrome characterized by a rapid decrease of kidney function, is a global health problem. Src family kinases (SFK) are proto-oncogenes that regulate diverse biological functions including mitochondrial function. Since mitochondrial dysfunction plays an important role in the development of AKI, and since unbalanced SFK activity causes mitochondrial dysfunction, the present study examined the role of SFK in AKI. Lipopolysaccharides (LPS) inhibited mitochondrial biogenesis and upregulated the expression of NGAL, a marker of tubular epithelial cell injury, in mouse proximal tubular epithelial (mProx) cells. These alterations were prevented by PP2, a pan SFK inhibitor. Importantly, PP2 pretreatment significantly ameliorated LPS-induced loss of kidney function and injury including inflammation and oxidative stress. The attenuation of LPS-induced AKI by PP2 was accompanied by the maintenance of mitochondrial biogenesis. LPS upregulated SFK, especially Fyn and Src, in mouse kidney as well as in mProx cells. These data suggest that Fyn and Src kinases are involved in the pathogenesis of LPS-induced AKI, and that inhibition of Fyn and Src kinases may have a potential therapeutic effect, possibly via improving mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Autophagy is a vacuolar, lysosomal degradation pathway for injured and damaged protein molecules and organelles in eukaryotic cells, which is controlled by nutrients and stress responses. Dysregulation of cellular autophagy may lead to various diseases such as neurodegenerative disease, obesity, cardiovascular disease, diabetes, and malignancies. Recently, natural compounds have come to attention for being able to modulate the autophagy pathway in cancer prevention, although the prospective role of autophagy in cancer treatment is very complex and not yet clearly elucidated. Numerous synthetic chemicals have been identified that modulate autophagy and are favorable candidates for cancer treatment, but they have adverse side effects. Therefore, different phytochemicals, which include natural compounds and their derivatives, have attracted significant attention for use as autophagy modulators in cancer treatment with minimal side effects. In the current review, we discuss the promising role of natural compounds in modulating the autophagy pathway to control and prevent cancer, and provide possible therapeutic options. [ABSTRACT FROM AUTHOR]

Beyond their significant contribution to the dietary and industrial supplies, marine algae are considered to be a potential source of some unique metabolites with diverse health benefits. The pharmacological properties, such as antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance and anti-amyloidogenic potentials of algal metabolites endorse their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis which are known to be implicated in the pathophysiology of neurodegenerative disorders and the associated complications after cerebral ischemia and brain injuries. As was evident in various preclinical studies, algal compounds conferred neuroprotection against a wide range of neurotoxic stressors, such as oxygen/glucose deprivation, hydrogen peroxide, glutamate, amyloid β, or 1-methyl-4-phenylpyridinium (MPP+) and, therefore, hold therapeutic promise for brain disorders. While a significant number of algal compounds with promising neuroprotective capacity have been identified over the last decades, a few of them have had access to clinical trials. However, the recent approval of an algal oligosaccharide, sodium oligomannate, for the treatment of Alzheimer's disease enlightened the future of marine algae-based drug discovery. In this review, we briefly outline the pathophysiology of neurodegenerative diseases and brain injuries for identifying the targets of pharmacological intervention, and then review the literature on the neuroprotective potentials of algal compounds along with the underlying pharmacological mechanism, and present an appraisal on the recent therapeutic advances. We also propose a rational strategy to facilitate algal metabolites-based drug development. [ABSTRACT FROM AUTHOR]