Hydroxychloroquine: Key therapeutic advances and emerging nanotechnological landscape for cancer mitigation.

Hydroxychloroquine (HCQ) is a unique class of medications that has been widely utilized for the treatment of cancer. HCQ plays a dichotomous role by inhibiting autophagy induced by the tumor microenvironment (TME). Preclinical studies support the use of HCQ for anti-cancer therapy, especially in combination with conventional anti-cancer treatments since they sensitize tumor cells to drugs, potentiating the therapeutic activity. However, clinical evidence has suggested poor outcomes for HCQ due to various obstacles, including non-specific distribution, low aqueous solubility and low bioavailability at target sites, transport across tissue barriers, and retinal toxicity. These issues are addressable via the integration of HCQ with nanotechnology to produce HCQ-conjugated nanomedicines. This review aims to discuss the pharmacodynamic, pharmacokinetic and antitumor properties of HCQ. Furthermore, the antitumor performance of the nanoformulated HCQ is also reviewed thoroughly, aiming to serve as a guide for the HCQ-based enhanced treatment of cancers. The nanoencapsulation or nanoconjugation of HCQ with nanoassemblies appears to be a promising method for reducing the toxicity and improving the antitumor efficacy of HCQ.

Editorial: Biofunctional Molecule Exploratory Research on Application in Food and Health.

Biofunctional molecules with pharmacological activities are reported in various fields of application, including in the pharmaceutical, cosmetics, nutraceuticals, agriculture, and food industries [...].

Targeting Immune Senescence in Atherosclerosis.

Atherosclerosis is one of the main underlying causes of cardiovascular diseases (CVD). It is associated with chronic inflammation and intimal thickening as well as the involvement of multiple cell types including immune cells. The engagement of innate or adaptive immune response has either athero-protective or atherogenic properties in exacerbating or alleviating atherosclerosis. In atherosclerosis, the mechanism of action of immune cells, particularly monocytes, macrophages, dendritic cells, and B- and T-lymphocytes have been discussed. Immuno-senescence is associated with aging, viral infections, genetic predispositions, and hyperlipidemia, which contribute to atherosclerosis. Immune senescent cells secrete SASP that delays or accelerates atherosclerosis plaque growth and associated pathologies such as aneurysms and coronary artery disease. Senescent cells undergo cell cycle arrest, morphological changes, and phenotypic changes in terms of their abundances and secretome profile including cytokines, chemokines, matrix metalloproteases (MMPs) and Toll-like receptors (TLRs) expressions. The senescence markers are used in therapeutics and currently, senolytics represent one of the emerging treatments where specific targets and clearance of senescent cells are being considered as therapy targets for the prevention or treatment of atherosclerosis.

Knowledge transfer of eLearning objects: Lessons learned from an intercontinental capacity building project.

BACKGROUND: Effective knowledge transfer of eLearning objects can hasten the adoption and dissemination of technology in teaching and learning. However, challenges exist which hinder inter-organisational knowledge transfer, particularly across continents. The ACoRD project aimed to transfer knowledge on digital learning development from UK/EU (provider) to Malaysian (receiver) higher education institutions (HEIs). This study explores the challenges encountered during the knowledge transfer process and lessons learned. METHODS: This is a qualitative study involving both the knowledge providers and receivers in focus group discussions (n = 25). Four focus group discussions were conducted in the early (n = 2) and mid-phase (n = 2) of the project by trained qualitative researchers using a topic guide designed to explore experiences and activities representing knowledge transfer in multi-institutional and multi-cultural settings. The interviews were audio-recorded, transcribed verbatim, and checked. The transcripts were analysed using thematic analysis. RESULTS: Five main themes emerged from this qualitative study: mismatched expectations between providers and receivers; acquiring new knowledge beyond the professional "comfort zone"; challenges in cascading newly acquired knowledge to colleagues and management; individual and organisational cultural differences; and disruption of knowledge transfer during the COVID-19 pandemic. CONCLUSION: This study highlights the need to create a conducive platform to facilitate continuous, timely and bi-directional needs assessment and feedback; this should be done in the early phase of the knowledge transfer process. The challenges and strategies identified in this study could guide more effective knowledge transfer between organisations and countries.

Sophorolipids-Bio-Based Antimicrobial Formulating Agents for Applications in Food and Health.

Sophorolipids are well-known glycolipid biosurfactants, produced mainly by non-pathogenic yeast species such as Candida bombicola with high yield. Its unique environmental compatibility and high biodegradable properties have made them a focus in the present review for their promising applications in diverse areas. This study aims to examine current research trends of sophorolipids and evaluate their applications in food and health. A literature search was conducted using different research databases including PubMed, ScienceDirect, EBSCOhost, and Wiley Online Library to identify studies on the fundamental mechanisms of sophorolipids and their applications in food and health. Studies have shown that various structural forms of sophorolipids exhibit different biological and physicochemical properties. Sophorolipids represent one of the most attractive biosurfactants in the industry due to their antimicrobial action against both Gram-positive and Gram-negative microorganisms for applications in food and health sectors. In this review, we have provided an overview on the fundamental properties of sophorolipids and detailed analysis of their applications in diverse areas such as food, agriculture, pharmaceutical, cosmetic, anticancer, and antimicrobial activities.

Uncovering incontinentia pigmenti: From DNA sequence to pathophysiology.

Incontinentia pigmenti (IP) is an X-linked dominant genodermatosis. The disease is known to be caused by recurrent deletion of exons 4-10 of the Inhibitor Of Nuclear Factor Kappa B Kinase Regulatory Subunit Gamma (IKBKG) gene located at the Xq28 chromosomal region, which encodes for NEMO/IKKgamma, a regulatory protein involved in the nuclear factor kappa B (NF-κB) signaling pathway. NF-κB plays a prominent role in the modulation of cellular proliferation, apoptosis, and inflammation. IKBKG mutation that results in a loss-of-function or dysregulated NF-κB pathway contributes to the pathophysiology of IP. Aside from typical skin characteristics such as blistering rash and wart-like skin growth presented in IP patients, other clinical manifestations like central nervous system (CNS) and ocular anomalies have also been detected. To date, the clinical genotype-phenotype correlation remains unclear due to its highly variable phenotypic expressivity. Thus, genetic findings remain an essential tool in diagnosing IP, and understanding its genetic profile allows a greater possibility for personalized treatment. IP is slowly and gradually gaining attention in research, but there is much that remains to be understood. This review highlights the progress that has been made in IP including the different types of mutations detected in various populations, current diagnostic strategies, IKBKG pathophysiology, genotype-phenotype correlation, and treatment strategies, which provide insights into understanding this rare mendelian disorder.

Cosmeceutical Therapy: Engaging the Repercussions of UVR Photoaging on the Skin's Circadian Rhythm.

Sunlight is an important factor in regulating the central circadian rhythm, including the modulation of our sleep/wake cycles. Sunlight had also been discovered to have a prominent influence on our skin's circadian rhythm. Overexposure or prolonged exposure to the sun can cause skin photodamage, such as the formation of irregular pigmentation, collagen degradation, DNA damage, and even skin cancer. Hence, this review will be looking into the detrimental effects of sunlight on our skin, not only at the aspect of photoaging but also at its impact on the skin's circadian rhythm. The growing market trend of natural-product-based cosmeceuticals as also caused us to question their potential to modulate the skin's circadian rhythm. Questions about how the skin's circadian rhythm could counteract photodamage and how best to maximize its biopotential will be discussed in this article. These discoveries regarding the skin's circadian rhythm have opened up a completely new level of understanding of our skin's molecular mechanism and may very well aid cosmeceutical companies, in the near future, to develop better products that not only suppress photoaging but remain effective and relevant throughout the day.

Triangulating the pharmacological properties of thymoquinone in regulating reactive oxygen species, inflammation, and cancer: Therapeutic applications and mechanistic pathways.

Cancer is a heterogeneous disease with high morbidity and mortality rate involving changes in redox balance and deregulation of redox signalling. For decades, studies have involved developing an effective cancer treatment to combat treatment resistance. As natural products such as thymoquinone have numerous health benefits, studies are also focusing on using them as a viable method for cancer treatment, as they have minimal toxic effects compared with standard cancer treatments. Thymoquinone studies have shown numerous mechanisms of action, such as regulation of reactive species interfering with DNA structure, modulating various potential targets and their signalling pathways as well as immunomodulatory effects in vitro and in vivo. Thymoquinone's anti-cancer effect is mainly due to the induction of apoptotic mechanisms, such as activation of caspases, downregulation of precancerous genes, inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), anti-tumour cell proliferation, ROS regulation, hypoxia and anti-metastasis. Insight into thymoquinone's potential as an alternative treatment for chemoprevention and inflammation can be accomplished via compiling these studies, to provide a better understanding on how and why it works, as well as its interactions with common chemotherapeutic treatments.

Unraveling the Immunopathogenesis and Genetic Variants in Vasculitis Toward Development of Personalized Medicine.

Leukocytoclastic vasculitis (LCV) is a systemic autoimmune disease characterized by the inflammation of the vascular endothelium. Cutaneous small vessel vasculitis (CSVV) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are two examples of LCV. Advancements in genomic technologies have identified risk haplotypes, genetic variants, susceptibility loci and pathways that are associated with vasculitis immunopathogenesis. The discovery of these genetic factors and their corresponding cellular signaling aberrations have enabled the development and use of novel therapeutic strategies for vasculitis. Personalized medicine aims to provide targeted therapies to individuals who show poor response to conventional interventions. For example, monoclonal antibody therapies have shown remarkable efficacy in achieving disease remission. Here, we discuss pathways involved in disease pathogenesis and the underlying genetic associations in different populations worldwide. Understanding the immunopathogenic pathways in vasculitis and identifying associated genetic variations will facilitate the development of novel and targeted personalized therapies for patients.

Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing.

Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.

Harnessing the Potential of CRISPR/Cas in Atherosclerosis: Disease Modeling and Therapeutic Applications.

Atherosclerosis represents one of the major causes of death globally. The high mortality rates and limitations of current therapeutic modalities have urged researchers to explore potential alternative therapies. The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system is commonly deployed for investigating the genetic aspects of Atherosclerosis. Besides, advances in CRISPR/Cas system has led to extensive options for researchers to study the pathogenesis of this disease. The recent discovery of Cas9 variants, such as dCas9, Cas9n, and xCas9 have been established for various applications, including single base editing, regulation of gene expression, live-cell imaging, epigenetic modification, and genome landscaping. Meanwhile, other Cas proteins, such as Cas12 and Cas13, are gaining popularity for their applications in nucleic acid detection and single-base DNA/RNA modifications. To date, many studies have utilized the CRISPR/Cas9 system to generate disease models of atherosclerosis and identify potential molecular targets that are associated with atherosclerosis. These studies provided proof-of-concept evidence which have established the feasibility of implementing the CRISPR/Cas system in correcting disease-causing alleles. The CRISPR/Cas system holds great potential to be developed as a targeted treatment for patients who are suffering from atherosclerosis. This review highlights the advances in CRISPR/Cas systems and their applications in establishing pathogenetic and therapeutic role of specific genes in atherosclerosis.

Exploring the use of virtual laboratory simulations before, during, and post COVID-19 recovery phase: An Animal Biotechnology case study.

This study presents an evaluation of integrating virtual laboratory simulations in assessment design of a biotechnology course at Taylor's University in Malaysia before, during and post-COVID recovery phases. The purpose was to investigate how virtual laboratory simulations were integrated as part of the assessments of a practical-embedded course-the aim being to evaluate students' acceptance and perception of using virtual simulation. A total of 46 students, across three different study cohorts (August 2019, March 2020, and August 2020) were evaluated different educational aspects of using virtual laboratory cases in a 4-week course within Animal Biotechnology. Overall, students regarded virtual laboratory simulation useful as part of their learning, and there is a significant increase in the level of acceptance before, during and post-COVID recovery phases. The study showed that across the different study cohorts, students perceived their confidence level in laboratory skills have been enhanced and that they can apply the skills in real-life situation. Interestingly, students (March and August 2020 cohort) who have not been exposed to the related laboratory session still perceived that the simulated activity provides clear explanation and realistic experience. Furthermore, it had been highlighted across the study cohorts that the quiz questions helped to enhance their understanding on the underlying principles of the laboratory techniques. The overall conclusion of this study was that structured simulation-based activities which provide clear instructions and explanation would support significant improvements in students learning.

Prioritising topics for developing e-learning resources in healthcare curricula: A comparison between students and educators using a modified Delphi survey.

BACKGROUND: Engaging students in the e-learning development process enhances the effective implementation of e-learning, however, students' priority on the topics for e-learning may differ from that of the educators. This study aims to compare the differences between the students and their educators in prioritising the topics in three healthcare curricula for reusable e-learning object (RLO) development. METHOD: A modified Delphi study was conducted among students and educators from University Malaya (UM), Universiti Putra Malaysia (UPM) and Taylor's University (TU) on three undergraduate programmes. In Round 1, participants were asked to select the topics from the respective syllabi to be developed into RLOs. Priority ranking was determined by using frequencies and proportions. The first quartile of the prioritised topics was included in Round 2 survey, which the participants were asked to rate the level of priority of each topic using a 5-point Likert scale. The mean score of the topics was compared between students and educators. RESULT: A total of 43 educators and 377 students participated in this study. For UM and TU Pharmacy, there was a mismatch in the prioritised topics between the students and educators. For UPM, both the educators and students have prioritised the same topics in both rounds. To harmonise the prioritisation of topics between students and educators for UM and TU Pharmacy, the topics with a higher mean score by both the students and educators were prioritised. CONCLUSION: The mismatch in prioritised topics between students and educators uncovered factors that might influence the prioritisation process. This study highlighted the importance of conducting needs assessment at the beginning of eLearning resources development.

In vitro evaluation of the involvement of Nrf2 in maslinic acid-mediated anti-inflammatory effects in atheroma pathogenesis.

AIMS: Maslinic acid (MA) is a naturally occurring pentacyclic triterpene known to exert cardioprotective effects. This study aims to investigate the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) for MA-mediated anti-inflammatory effects in atheroma pathogenesis in vitro, including evaluation of tumor necrosis factor-alpha (TNF-α)-induced monocyte recruitment, oxidized low-density lipoprotein (oxLDL)-induced scavenger receptors expression, and nuclear factor-kappa B (NF-ĸB) activity in human umbilical vein endothelial cells (HUVECS) and human acute monocytic leukemia cell line (THP-1) macrophages. MATERIALS AND METHODS: An in vitro monocyte recruitment model utilizing THP-1 and HUVECs was developed to evaluate TNF-α-induced monocyte adhesion and trans-endothelial migration. To study the role of Nrf2 for MA-mediated anti-inflammatory effects, Nrf2 inhibitor ML385 was used as the pharmacological inhibitor. The expression of Nrf2, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 36 (CD36), and scavenger receptor type A (SR-A) in HUVECs and THP-1 macrophages were investigated using RT-qPCR and Western blotting. The NF-κB activity was determined using NF-κB (p65) Transcription Factor Assay Kit. KEY FINDINGS: The results showed opposing effects of MA on Nrf2 expression in HUVECs and THP-1 macrophages. MA suppressed TNF-α-induced Nrf2 expression in HUVECs, but enhanced its expression in THP-1 macrophages. Combined effects of MA and ML385 suppressed MCP-1, VCAM-1, and SR-A expressions. Intriguingly, at the protein level, ML385 selectively inhibited SR-A but enhanced CD36 expression. Meanwhile, ML385 further enhanced MA-mediated inhibition of NF-κB activity in HUVECs. This effect, however, was not observed in THP-1 macrophages. SIGNIFICANCE: MA attenuated foam cell formation by suppressing VCAM-1, MCP-1, and SR-A expression, as well as NF-κB activity, possibly through Nrf2 inhibition. The involvement of Nrf2 for MA-mediated anti-inflammatory effects however differs between HUVECs and macrophages. Future investigations are warranted for a detailed evaluation of the contributing roles of Nrf2 in foam cells formation.

Microalgae as Potential Anti-Inflammatory Natural Product Against Human Inflammatory Skin Diseases.

The skin is the first line of defense against pathogen and other environmental pollutant. The body is constantly exposed to reactive oxygen species (ROS) that stimulates inflammatory process in the skin. Many studies have linked ROS to various inflammatory skin diseases. Patients with skin diseases face various challenges with inefficient and inappropriate treatment in managing skin diseases. Overproduction of ROS in the body will result in oxidative stress which will lead to various cellular damage and alter normal cell function. Multiple signaling pathways are seen to have significant effects during ROS-mediated oxidative stress. In this review, microalgae have been selected as a source of natural-derived antioxidant to combat inflammatory skin diseases that are prominent in today's society. Several studies have demonstrated that bioactive compounds isolated from microalgae have anti-inflammation and anti-oxidative properties that can help remedy various skin diseases. These compounds are able to inhibit production of pro-inflammatory cytokines and reduce the expression of inflammatory genes. Bioactive compounds from microalgae work in action by altering enzyme activities, regulating cellular activities, targeting major signaling pathways related to inflammation.

Hyaluronic Acid-Mediated Drug Delivery System Targeting for Inflammatory Skin Diseases: A Mini Review.

Hyaluronic acid (HA), a major component of extracellular matrix has been widely applied in pharmaceutical and cosmetic industries due to its reported pharmacological properties. Various types of HA drug delivery system including nanoparticles, cryogel-based formulations, microneedle patches, and nano-emulsions were developed. There are studies reporting that several HA-based transdermal delivery systems exhibit excellent biocompatibility, enhanced permeability and efficient localized release of anti-psoriasis drugs and have shown to inhibit psoriasis-associated skin inflammation. Similarly HA is found in abundant at epidermis of atopic dermatitis (AD) suggesting its role in atopic AD pathology. Anti-allergenic effect of atopic eczema can be achieved through the inhibition of CD44 and protein kinase C alpha (PKCα) interaction by HA. Herein, we aim to evaluate the current innovation on HA drug delivery system and the other potential applications of HA in inflammatory skin diseases, focusing on atopic dermatitis and psoriasis. HA is typically integrated into different delivery systems including nanoparticles, liposomes, ethosomes and microneedle patches in supporting drug penetration through the stratum corneum layer of the skin. For instance, ethosomes and microneedle delivery system such as curcumin-loaded HA-modified ethosomes were developed to enhance skin retention and delivery of curcumin to CD44-expressing psoriatic cells whereas methotrexate-loaded HA-based microneedle was shown to enhance skin penetration of methotrexate to alleviate psoriasis-like skin inflammation. HA-based nanoparticles and pluronic F-127 based dual responsive (pH/temperature) hydrogels had been described to enhance drug permeation through and into the intact skin for AD treatment.

Angelicin-A Furocoumarin Compound With Vast Biological Potential.

Angelicin, a member of the furocoumarin group, is related to psoralen which is well known for its effectiveness in phototherapy. The furocoumarins as a group have been studied since the 1950s but only recently has angelicin begun to come into its own as the subject of several biological studies. Angelicin has demonstrated anti-cancer properties against multiple cell lines, exerting effects via both the intrinsic and extrinsic apoptotic pathways, and also demonstrated an ability to inhibit tubulin polymerization to a higher degree than psoralen. Besides that, angelicin too demonstrated anti-inflammatory activity in inflammatory-related respiratory and neurodegenerative ailments via the activation of NF-κB pathway. Angelicin also showed pro-osteogenesis and pro-chondrogenic effects on osteoblasts and pre-chondrocytes respectively. The elevated expression of pro-osteogenic and chondrogenic markers and activation of TGF-ß/BMP, Wnt/ß-catenin pathway confirms the positive effect of angelicin bone remodeling. Angelicin also increased the expression of estrogen receptor alpha (ERα) in osteogenesis. Other bioactivities, such as anti-viral and erythroid differentiating properties of angelicin, were also reported by several researchers with the latter even displaying an even greater aptitude as compared to the commonly prescribed drug, hydroxyurea, which is currently on the market. Apart from that, recently, a new application for angelicin against periodontitis had been studied, where reduction of bone loss was indirectly caused by its anti-microbial properties. All in all, angelicin appears to be a promising compound for further studies especially on its mechanism and application in therapies for a multitude of common and debilitating ailments such as sickle cell anaemia, osteoporosis, cancer, and neurodegeneration. Future research on the drug delivery of angelicin in cancer, inflammation and erythroid differentiation models would aid in improving the bioproperties of angelicin and efficacy of delivery to the targeted site. More in-depth studies of angelicin on bone remodeling, the pro-osteogenic effect of angelicin in various bone disease models and the anti-viral implications of angelicin in periodontitis should be researched. Finally, studies on the binding of angelicin toward regulatory genes, transcription factors, and receptors can be done through experimental research supplemented with molecular docking and molecular dynamics simulation.

Anticancer Mechanisms of Bioactive Peptides.

Despite technological advancement, there is no 100% effective treatment against metastatic cancer. Increasing resistance of cancer cells towards chemotherapeutic drugs along with detrimental side effects remained a concern. Thus, the urgency in developing new anticancer agents has been raised. Anticancer peptides have been proven to display potent activity against a wide variety of cancer cells. Several mode of actions describing their cytostatic and cytotoxic effect on cancer cells have been proposed which involves cell surface binding leading to membranolysis or internalization to reach their intracellular target. Understanding the mechanism of action of these anticancer peptides is important in achieving full therapeutic success. In the present article, we discuss the anticancer action of peptides accompanied by the mechanisms underpinning their toxicity to cancer cells.