A High-Performance Passive Radiative Cooling Metafabric with Janus Wettability and Thermal Conduction.

With the development of industry and global warming, passive radiative cooling textiles have recently drawn great interest owing to saving energy consumption and preventing heat-related illnesses. Nevertheless, existing cooling textiles often lack efficient sweat management capacity and wearable comfort under many practical conditions. Herein, a hierarchical cooling metafabric that integrates passive radiation, thermal conduction, sweat evaporation, and excellent wearable comfort is reported through an electrospinning strategy. The metafabric presents excellent solar reflectivity (99.7%, 0.3-2.5 µm) and selective infrared radiation (92.4%, 8-13 µm), given that the unique optical nature of materials and wettability gradient/micro-nano hierarchical structure design. The strong moisture-wicking effect (water vapor transmission (WVT) of 2985 g m-2 d-1 and directional water transport index (R) of 1029.8%) and high heat-conduction capacity can synergistically enhance the radiative cooling efficiency of the metafabric. The outdoor experiment reveals that the metafabric can obtain cooling temperatures of 13.8 °C and 19.3 °C in the dry and sweating state, respectively. Meanwhile, the metafabric saves ≈19.3% of annual energy consumption compared with the buildings with HAVC systems in Shanghai. The metafabric also demonstrates desirable breathability, mechanical strength, and washability. The cost-effective and high-performance metafabric may offer a novel avenue for developing next-generation personal cooling textiles.

Comparative interactome mapping of Tau-protein in classical and rapidly progressive Alzheimer's disease identifies subtype-specific pathways.

AIMS: Tau is a key player in Alzheimer's disease (AD) and other Tauopathies. Tau pathology in the brain directly correlates with neurodegeneration in AD. The recent identification of a rapid variant of AD demands an urgent need to uncover underlying mechanisms leading to differential progression in AD. Accordingly, we aimed to dissect the underlying differential mechanisms of toxicity associated with the Tau protein in AD subtypes and to find out subtype-dependent biomarkers and therapeutic targets. METHODS: To identify and characterise subtype-specific Tau-associated mechanisms of pathology, we performed comparative interactome mapping of Tau protein in classical AD (cAD) and rapidly progressive AD (rpAD) cases using co-immunoprecipitation coupled with quantitative mass spectrometry. The mass spectrometry data were extensively analysed using several bioinformatics approaches. RESULTS: The comparative interactome mapping of Tau protein revealed distinct and unique interactors (DPYSL4, ARHGEF2, TUBA4A and UQCRC2) in subtypes of AD. Interestingly, an analysis of the Tau-interacting proteins indicated enrichment of mitochondrial organisation processes, including negative regulation of mitochondrion organisation, mitochondrial outer membrane permeabilisation involved in programmed cell death, regulation of autophagy of mitochondrion and necroptotic processes, specifically in the rpAD interactome. While, in cAD, the top enriched processes were related to oxidation-reduction process, transport and monocarboxylic acid metabolism. CONCLUSIONS: Overall, our results provide a comprehensive map of Tau-interacting protein networks in a subtype-dependent manner and shed light on differential functions/pathways in AD subtypes. This comprehensive map of the Tau-interactome has provided subsets of disease-related proteins that can serve as novel biomarkers/biomarker panels and new drug targets.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Interplay of oxidative stress, cellular communication and signaling pathways in cancer.

Cancer remains a significant global public health concern, with increasing incidence and mortality rates worldwide. Oxidative stress, characterized by the production of reactive oxygen species (ROS) within cells, plays a critical role in the development of cancer by affecting genomic stability and signaling pathways within the cellular microenvironment. Elevated levels of ROS disrupt cellular homeostasis and contribute to the loss of normal cellular functions, which are associated with the initiation and progression of various types of cancer. In this review, we have focused on elucidating the downstream signaling pathways that are influenced by oxidative stress and contribute to carcinogenesis. These pathways include p53, Keap1-NRF2, RB1, p21, APC, tumor suppressor genes, and cell type transitions. Dysregulation of these pathways can lead to uncontrolled cell growth, impaired DNA repair mechanisms, and evasion of cell death, all of which are hallmark features of cancer development. Therapeutic strategies aimed at targeting oxidative stress have emerged as a critical area of investigation for molecular biologists. The objective is to limit the response time of various types of cancer, including liver, breast, prostate, ovarian, and lung cancers. By modulating the redox balance and restoring cellular homeostasis, it may be possible to mitigate the damaging effects of oxidative stress and enhance the efficacy of cancer treatments. The development of targeted therapies and interventions that specifically address the impact of oxidative stress on cancer initiation and progression holds great promise in improving patient outcomes. These approaches may include antioxidant-based treatments, redox-modulating agents, and interventions that restore normal cellular function and signaling pathways affected by oxidative stress. In summary, understanding the role of oxidative stress in carcinogenesis and targeting this process through therapeutic interventions are of utmost importance in combating various types of cancer. Further research is needed to unravel the complex mechanisms underlying oxidative stress-related pathways and to develop effective strategies that can be translated into clinical applications for the management and treatment of cancer. Video Abstract.

Glyphosate in the environment: interactions and fate in complex soil and water settings, and (phyto) remediation strategies.

Glyphosate (Gly) and its formulations are broad-spectrum herbicides globally used for pre- and post-emergent weed control. Glyphosate has been applied to terrestrial and aquatic ecosystems. Critics have claimed that Gly-treated plants have altered mineral nutrition and increased susceptibility to plant pathogens because of Gly ability to chelate divalent metal cations. Still, the complete resistance of Gly indicates that chelation of metal cations does not play a role in herbicidal efficacy or have a substantial impact on mineral nutrition. Due to its extensive and inadequate use, this herbicide has been frequently detected in soil (2 mg kg-1, European Union) and in stream water (328 µg L-1, USA), mostly in surface (7.6 µg L-1, USA) and groundwater (2.5 µg L-1, Denmark). International Agency for Research on Cancer (IARC) already classified Gly as a category 2 A carcinogen in 2016. Therefore, it is necessary to find the best degradation techniques to remediate soil and aquatic environments polluted with Gly. This review elucidates the effects of Gly on humans, soil microbiota, plants, algae, and water. This review develops deeper insight toward the advances in Gly biodegradation using microbial communities. This review provides a thorough understanding of Gly interaction with mineral elements and its limitations by interfering with the plants biochemical and morphological attributes.

Glyphosate (Gly) contamination in water, soil, and crops is an eminent threat globally. Various advanced and integrated approaches have been reported to remediate Gly contamination from the water-soil-crop system. This review elucidates the effects of Gly on human health, soil microbial communities, plants, algae, and water. This review develops deeper insight into the advances in Gly biodegradation using microbial communities, particularly soil microbiota. This review provides a brief understanding of Gly interaction with mineral elements and its limitations in interfering with the plants biochemical and morphological attributes.

Targeted therapy using nanocomposite delivery systems in cancer treatment: highlighting miR34a regulation for clinical applications.

The clinical application of microRNAs in modern therapeutics holds great promise to uncover molecular limitations and conquer the unbeatable castle of cancer metastasis. miRNAs play a decisive role that regulating gene expression at the post-transcription level while controlling both the stability and translation capacity of mRNAs. Specifically, miR34a is a master regulator of the tumor suppressor gene, cancer progression, stemness, and drug resistance at the cell level in p53-dependent and independent signaling. With changing, trends in nanotechnology, in particular with the revolution in the field of nanomedicine, nano drug delivery systems have emerged as a prominent strategy in clinical practices coupled with miR34a delivery. Recently, it has been observed that forced miR34a expression in human cancer cell lines and model organisms limits cell proliferation and metastasis by targeting several signaling cascades, with various studies endorsing that miR34a deregulation in cancer cells modulates apoptosis and thus requires targeted nano-delivery systems for cancer treatment. In this sense, the present review aims to provide an overview of the clinical applications of miR34a regulation in targeted therapy of cancer.

Cellular signaling modulated by miRNA-3652 in ovarian cancer: unveiling mechanistic pathways for future therapeutic strategies.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play pivotal roles in regulating gene expression and have been implicated in the pathogenesis of numerous cancers. miRNA-3652, though relatively less explored, has recently emerged as a potential key player in ovarian cancer's molecular landscape. This review aims to delineate the functional significance and tumor progression role of miRNA-3652 in ovarian cancer, shedding light on its potential as both a diagnostic biomarker and therapeutic target. A comprehensive literature search was carried out using established databases, the focus was on articles that reported the role of miRNA-3652 in ovarian cancer, encompassing mechanistic insights, functional studies, and its association with clinical outcomes. This updated review highlighted that miRNA-3652 is intricately involved in ovarian cancer cell proliferation, migration, and invasion, its dysregulation was linked to altered expression of critical genes involved in tumor growth and metastasis; furthermore, miRNA-3652 expression levels were found to correlate with clinical stages, prognosis, and response to therapy in ovarian cancer patients. miRNA-3652 holds significant promise as a vital molecular player in ovarian cancer's pathophysiology. Its functional role and impact on tumor progression make it a potential candidate for diagnostic and therapeutic applications in ovarian cancer. Given the pivotal role of miRNA-3652 in ovarian cancer, future studies should emphasize in-depth mechanistic explorations, utilizing advanced genomic and proteomic tools. Collaboration between basic scientists and clinicians will be vital to translating these findings into innovative diagnostic and therapeutic strategies, ultimately benefiting ovarian cancer patients. Video Abstract.

The Electronic Properties of Cadmium Naphthalene Diimide Coordination Complex.

The computational simulations for electronic properties of cadmium (Cd) coordinated L-alanine NDI ligand (H2-l-ala NDI) based complex are the focus of this research. For the first time, the Cd-NDI complex (monomer) has been produced using water as the solvent; this is a new approach to synthesizing the Cd-NDI complex that has not been reported yet. Along with crystallography and Hirsch field analysis, CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets were used, and in-depth characterisation of the Cd-NDI complex by following DFT and TD-DFT hypothetical simulations. Hyperpolarizabilities, frontier molecular orbitals (FMOs), the density of states (DOS), dipole moment (µ), electron density distribution map (EDDM), transition density matrix (TDM), molecular electrostatic potential (MEP), electron-hole analysis (EHA), and electrical conductivity (σ) have all been studied regarding the Cd-NDI complex. The vibrational frequencies and types of interaction are studied using infrared (IR) and non-covalent interaction (NCI) analysis with iso-surface. In comparison to the Cd-NDI complex with 2.61, 2.42 eV Eg (using CAM-B3LYP/LANL2DZ and B3LYP/LANL2MB basis sets, respectively) and 376 nm λmax, (in case of B3LYP/LANL2MB λmax is higher), H2-l-ala NDI have 3.387 eV Eg and 375 nm λmax, metal-ligand coordination in complex dramatically altered charge transfer properties, such as narrowing band gap (Eg). Based on the electronic properties analysis of Cd-NDI complex, it is predicted that the Cd-NDI complex will have a spectacular (nonlinear optical) NLO response. The Cd-NDI complex is discovered to be advantageous for the creation of future nanoscale devices due to the harmony between the Cd metal and H2-l-ala NDI, in addition to their influences on NLO characteristics.

Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation.

Recent technological advances in nanoscience and material designing have led to the development of point-of-care devices for biomolecule sensing and cancer diagnosis. In situ and portable sensing devices for bedside, diagnosis can effectively improve the patient's clinical outcomes and reduce the mortality rate. Detection of exosomal RNAs by immuno-biochip with increased sensitivity and specificity to diagnose cancer has raised the understanding of the tumor microenvironment and many other technology-based biosensing devices hold great promise for clinical innovations to conquer the unbeatable fort of cancer metastasis. Electrochemical biosensors are the most sensitive category of biomolecule detection sensors with significantly low concentrations down to the atomic level. In this sense, this review addresses the recent advances in cancer detection and diagnosis by developing significant biological sensing devices that are believed to have better sensing potential than existing facilities.

Myricetin: targeting signaling networks in cancer and its implication in chemotherapy.

The gaps between the complex nature of cancer and therapeutics have been narrowed down due to extensive research in molecular oncology. Despite gathering massive insight into the mysteries of tumor heterogeneity and the molecular framework of tumor cells, therapy resistance and adverse side effects of current therapeutic remain the major challenge. This has shifted the attention towards therapeutics with less toxicity and high efficacy. Myricetin a natural flavonoid has been under the spotlight for its anti-cancer, anti-oxidant, and anti-inflammatory properties. The cutting-edge molecular techniques have shed light on the interplay between myricetin and dysregulated signaling cascades in cancer progression, invasion, and metastasis. However, there are limited data available regarding the nano-delivery platforms composed of myricetin in cancer. In this review, we have provided a comprehensive detail of myricetin-mediated regulation of different cellular pathways, its implications in cancer prevention, preclinical and clinical trials, and its current available nano-formulations for the treatment of various cancers.

New-onset and relapsed liver diseases following COVID-19 vaccination: a systematic review.

BACKGROUND: Liver diseases post-COVID-19 vaccination is extremely rare but can occur. A growing body of evidence has indicated that portal vein thrombosis, autoimmune hepatitis, raised liver enzymes and liver injuries, etc., may be potential consequence of COVID-19 vaccines. OBJECTIVES: To describe the results of a systematic review for new-onset and relapsed liver disease following COVID-19 vaccination. METHODS: For this systematic review, we searched Proquest, Medline, Embase, PubMed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses PRISMA guideline for studies on the incidence of new onset or relapsed liver diseases post-COVID-19 vaccination, published from December 1, 2020 to July 31, 2022, with English language restriction. RESULTS: Two hundred seventy-five cases from one hundred and eighteen articles were included in the qualitative synthesis of this systematic review. Autoimmune hepatitis (138 cases) was the most frequent pathology observed post-COVID-19 vaccination, followed by portal vein thrombosis (52 cases), raised liver enzymes (26 cases) and liver injury (21 cases). Other cases include splanchnic vein thrombosis, acute cellular rejection of the liver, jaundice, hepatomegaly, acute hepatic failure and hepatic porphyria. Mortality was reported in any of the included cases for acute hepatic failure (n = 4, 50%), portal vein thrombosis (n = 25, 48.1%), splanchnic vein thrombosis (n = 6, 42.8%), jaundice (n = 1, 12.5%), raised liver enzymes (n = 2, 7.7%), and autoimmune hepatitis (n = 3, 2.2%). Most patients were easily treated without any serious complications, recovered and did not require long-term hepatic therapy. CONCLUSION: Reported evidence of liver diseases post-COIVD-19 vaccination should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively very small in relation to the hundreds of millions of vaccinations that have occurred and the protective benefits offered by COVID-19 vaccination far outweigh the risks.

Updates on Measles Incidence and Eradication: Emphasis on the Immunological Aspects of Measles Infection.

Measles is an RNA virus infectious disease mainly seen in children. Despite the availability of an effective vaccine against measles, it remains a health issue in children. Although it is a self-limiting disease, it becomes severe in undernourished and immune-compromised individuals. Measles infection is associated with secondary infections by opportunistic bacteria due to the immunosuppressive effects of the measles virus. Recent reports highlight that measles infection erases the already existing immune memory of various pathogens. This review covers the incidence, pathogenesis, measles variants, clinical presentations, secondary infections, elimination of measles virus on a global scale, and especially the immune responses related to measles infection.

Clinical applications of artificial intelligence and machine learning in cancer diagnosis: looking into the future.

Artificial intelligence (AI) is the use of mathematical algorithms to mimic human cognitive abilities and to address difficult healthcare challenges including complex biological abnormalities like cancer. The exponential growth of AI in the last decade is evidenced to be the potential platform for optimal decision-making by super-intelligence, where the human mind is limited to process huge data in a narrow time range. Cancer is a complex and multifaced disorder with thousands of genetic and epigenetic variations. AI-based algorithms hold great promise to pave the way to identify these genetic mutations and aberrant protein interactions at a very early stage. Modern biomedical research is also focused to bring AI technology to the clinics safely and ethically. AI-based assistance to pathologists and physicians could be the great leap forward towards prediction for disease risk, diagnosis, prognosis, and treatments. Clinical applications of AI and Machine Learning (ML) in cancer diagnosis and treatment are the future of medical guidance towards faster mapping of a new treatment for every individual. By using AI base system approach, researchers can collaborate in real-time and share knowledge digitally to potentially heal millions. In this review, we focused to present game-changing technology of the future in clinics, by connecting biology with Artificial Intelligence and explain how AI-based assistance help oncologist for precise treatment.

Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment.

Cancer is a complex disease orchestrated by various extrinsic and intrinsic pathways. In recent years, there has been a keen interest towards the development of natural extracts-based cancer therapeutics with minimum adverse effects. In pursuit of effective strategy, a wide variety of natural products-derived compounds have been addressed for their anticancer effects. Apigenin is a naturally-occurring flavonoid present abundantly in various fruits and vegetables. Decades of research have delineated the pharmacological and biological properties of apigenin. Specifically, the apigenin-mediated anticancer activities have been documented in various types of cancer, but the generalized scientific evidence encompassing various molecular interactions and processes, such as regulation of the apoptotic machinery, aberrant cell signaling and oncogenic protein network have not been comprehensively covered. In this sense, in this review we have attempted to focus on the apigenin-mediated regulation of oncogenic pathways in various cancers. We have also addressed the cutting-edge research which has unveiled the remarkable abilities of apigenin to interact with microRNAs to modulate key cellular processes, with special emphasis on the nano-formulations of apigenin that can help their targeted delivery and can be a therapeutic solution for the treatment of various cancers.

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers.

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

Role of plant growth promoting rhizobacteria in the alleviation of lead toxicity to Pisum sativum L.

Plant-microbe interaction is a significant tool to tackle heavy metals problem in the soil. A pot trial was conducted to evaluate the efficiency of lead tolerant rhizobacteria in improving pea growth under Pb stress. Lead sulfate (PbSO4) was used for spiking (250, 500, and 750 mg kg-1). Results indicated that inoculation with Pb-tolerant PGPR strain not only alleviated the harmful impacts of Pb on plant growth but also immobilized it in the soil. PGPR in the presence of Pb at concentrations of 0, 250, 500 and 750 mg kg-1, increased shoot and root lengths by 21, 15, 18% and 72, 80, 84%, respectively, than uninoculated control. Moreover, fresh biomass of shoots and roots were also increased by 51, 45, 35% and 57, 101, 139% respectively, at Pb concentrations of 250, 500 and 750 mg kg-1. In addition, PGPR inoculation also reduced Pb concentration in the roots and shoots by 57, 55, 49% and 70, 56 and 58% respectively, than uninoculated control. So, PGPR proved to be an efficient option for reducing Pb mobility and can be effectively used for its phytostabilization. Novelty statementLead (Pb) is highly noxious and second most toxic element in the nature having high persistence. It ranks 1st in the priority list of hazardous substances and causes adverse effects after its entry into the living system. So, its remediation is inevitable. Plant growth promoting rhizobacteria (PGPR) possess the potential to not only survive under stressed environments, but also promote plant growth on account of their different plant growth promoting mechanisms.Most researchers have worked on its bioaccumulation in plant body. This study however, used pea as a test crop and caused Pb phytostabilization and thereby, suppressed its entry in the above-ground plant parts.

New perspectives and future directions in the treatment of heart failure.

The management of heart failure has changed significantly over the last 30 years, leading to improvements in the quality of life and outcomes, at least for patients with a substantially reduced left ventricular ejection fraction (HFrEF). This has been made possible by the identification of various pathways leading to the development and progression of heart failure, which have been successfully targeted with effective therapies. Meanwhile, many other potential targets of treatment have been identified, and the list is constantly expanding. In this review, we summarise planned and ongoing trials exploring the potential benefit, or harm, of old and new pharmacological interventions that might offer further improvements in treatment for those with HFrEF and extend success to the treatment of patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and other heart failure phenotypes.

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer.

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.

ZnO-Templated Selenized and Phosphorized Cobalt-Nickel Oxide Microcubes as Rapid Alkaline Water Oxidation Electrocatalysts.

Oxygen electrocatalysis is of remarkable significance for electrochemical energy storage and conversion technologies, together with fuel cells, metal-air batteries, and water splitting devices. Substituting noble metal-based electrocatalysts by decidedly effective and low-cost metal-based oxygen electrocatalysts is imperative for the commercial application of these technologies. Herein, a novel strategy is presented to fabricate selenized and phosphorized porous cobalt-nickel oxide microcubes by using a sacrificial ZnO spherical template and the resulting microcubes are employed as an oxygen evolution reaction (OER) electrocatalyst. The selenized samples manifest desirable and robust OER performance, with comparable overpotential at 10 mA cm-2 (312 mV) as RuO2 (308 mV) and better activity when the current reaches 13.7 mA cm-2 . The phosphorized samples exhibit core-shell structure with low-crystalline oxides inside amorphous phosphides, which ensures superior activity than RuO2 with the same overpotential (at 10 mA cm-2 ) yet lower Tafel slope. Such a surface doping method possibly will provide inspiration for engineering electrocatalysts applied in water oxidation.

Natural Product Mediated Regulation of Death Receptors and Intracellular Machinery: Fresh from the Pipeline about TRAIL-Mediated Signaling and Natural TRAIL Sensitizers.

Rapidly developing resistance against different therapeutics is a major stumbling block in the standardization of therapy. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated signaling has emerged as one of the most highly and extensively studied signal transduction cascade that induces apoptosis in cancer cells. Rapidly emerging cutting-edge research has helped us to develop a better understanding of the signaling machinery involved in inducing apoptotic cell death. However, excitingly, cancer cells develop resistance against TRAIL-induced apoptosis through different modes. Loss of cell surface expression of TRAIL receptors and imbalance of stoichiometric ratios of pro- and anti-apoptotic proteins play instrumental roles in rewiring the machinery of cancer cells to develop resistance against TRAIL-based therapeutics. Natural products have shown excellent potential to restore apoptosis in TRAIL-resistant cancer cell lines and in mice xenografted with TRAIL-resistant cancer cells. Significantly refined information has previously been added and continues to enrich the existing pool of knowledge related to the natural-product-mediated upregulation of death receptors, rebalancing of pro- and anti-apoptotic proteins in different cancers. In this mini review, we will set spotlight on the most recently published high-impact research related to underlying mechanisms of TRAIL resistance and how these deregulations can be targeted by natural products to restore TRAIL-mediated apoptosis in different cancers.