Search

Diabetes, characterized by elevated blood sugar levels, poses significant health and economic risks, correlating with complications like cardiovascular disease, kidney failure, and blindness. Dipeptidyl peptidase-4 (DPP-4), also referred to as T-cell activation antigen CD26 (EC 3.4.14.5.), plays a crucial role in glucose metabolism and immune function. Inhibiting DPP-4 was anticipated as a potential new therapy for diabetes. Therefore, identification of plant-based natural inhibitors of DPP-4 would help in eradicating diabetes worldwide. Here, for the identification of the potential natural inhibitors of DPP-4, we developed a phytochemicals library consisting of over 6000 phytochemicals detected in 81 medicinal plants that exhibited anti-diabetic potency. The library has been docked against the target proteins, where isorhamnetin, Benzyl 5-Amino-5-deoxy-2,3-O-isopropyl-alpha-D-mannofuranoside (DTXSID90724586), and 5-Oxo-7-[4-(trifluoromethyl) phenyl]-4H,6H,7H-[1,2]thiazolo[4,5-b]pyridine 3-carboxylic acid (CHEMBL3446108) showed binding affinities of −8.5, −8.3, and −8.3 kcal/mol, respectively. These compounds exhibiting strong interactions with DPP-4 active sites (Glu205, Glu206, Tyr547, Trp629, Ser630, Tyr662, His740) were identified. ADME/T and bioactivity predictions affirmed their pharmacological safety. Density functional theory calculations assessed stability and reactivity, while molecular dynamics simulations demonstrated persistent stability. Analyzing parameters like RMSD, RG, RMSF, SASA, H-bonds, MM-PBSA, and FEL confirmed stable protein–ligand compound formation. Principal component analysis provided structural variation insights. Our findings suggest that those compounds might be possible candidates for developing novel inhibitors targeting DPP-4 for treating diabetes. [ABSTRACT FROM AUTHOR]

Simple Summary: Heat shock proteins (HSPs) are extensively distributed throughout cells. They play a crucial role as molecular chaperones and regulate various cellular processes, such as metabolism, growth, differentiation, cell signaling, and programmed cell death. However, in cancers, HSPs are frequently overexpressed and associated with tumor advancement and metastasis, as well as in acquiring drug resistance against chemotherapeutic agents, leading to poor prognosis. Thus, the expression of HSPs can be modulated to imitate the cellular response against cancer cells by targeting the tumor microenvironment through different mechanisms. For instance, HSPs bind to antigens (peptides) associated with tumors, forming a complex that is easily recognized as an antigen-presenting cell (APC), leading to specific antitumor responses. This review summarizes and discusses recent advances, perspectives, and involvement of HSPs, including small and large HSPs, as well as the molecular mechanisms underlying tumor progression and metastasis. This study may offer new insights into the development of safer and more effective anticancer therapeutics. Heat shock proteins (HSPs) are developmentally conserved families of protein found in both prokaryotic and eukaryotic organisms. HSPs are engaged in a diverse range of physiological processes, including molecular chaperone activity to assist the initial protein folding or promote the unfolding and refolding of misfolded intermediates to acquire the normal or native conformation and its translocation and prevent protein aggregation as well as in immunity, apoptosis, and autophagy. These molecular chaperonins are classified into various families according to their molecular size or weight, encompassing small HSPs (e.g., HSP10 and HSP27), HSP40, HSP60, HSP70, HSP90, and the category of large HSPs that include HSP100 and ClpB proteins. The overexpression of HSPs is induced to counteract cell stress at elevated levels in a variety of solid tumors, including anticancer chemotherapy, and is closely related to a worse prognosis and therapeutic resistance to cancer cells. HSPs are also involved in anti-apoptotic properties and are associated with processes of cancer progression and development, such as metastasis, invasion, and cell proliferation. This review outlines the previously mentioned HSPs and their significant involvement in diverse mechanisms of tumor advancement and metastasis, as well as their contribution to identifying potential targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is one of the most significant staple foods worldwide. Carbohydrates, proteins, vitamins, and minerals are just a few of the many nutrients found in domesticated rice. Ensuring high and constant rice production is vital to facilitating human food supplies, as over three billion people around the globe rely on rice as their primary source of dietary intake. However, the world's rice production and grain quality have drastically declined in recent years due to the challenges posed by global climate change and abiotic stress-related aspects, especially drought, heat, cold, salt, submergence, and heavy metal toxicity. Rice's reduced photosynthetic efficiency results from insufficient stomatal conductance and natural damage to thylakoids and chloroplasts brought on by abiotic stressor-induced chlorosis and leaf wilting. Abiotic stress in rice farming can also cause complications with redox homeostasis, membrane peroxidation, lower seed germination, a drop in fresh and dry weight, necrosis, and tissue damage. Frequent stomatal movements, leaf rolling, generation of reactive oxygen radicals (RORs), antioxidant enzymes, induction of stress-responsive enzymes and protein-repair mechanisms, production of osmolytes, development of ion transporters, detoxifications, etc., are recorded as potent morphological, biochemical and physiological responses of rice plants under adverse abiotic stress. To develop cultivars that can withstand multiple abiotic challenges, it is necessary to understand the molecular and physiological mechanisms that contribute to the deterioration of rice quality under multiple abiotic stresses. The present review highlights the strategic defense mechanisms rice plants adopt to combat abiotic stressors that substantially affect the fundamental morphological, biochemical, and physiological mechanisms. [ABSTRACT FROM AUTHOR]

Pharmaceutical companies are investigating more source matrices for natural bioactive chemicals. Friedelin (friedelan-3-one) is a pentacyclic triterpene isolated from various plant species from different families as well as mosses and lichen. The fundamental compounds of these friedelane triterpenoids are abundantly found in cork tissues and leaf materials of diverse plant genera such as Celastraceae, Asteraceae, Fabaceae, and Myrtaceae. They possess many pharmacological effects, including anti-inflammatory, antioxidant, anticancer, and antimicrobial activities. Friedelin also has an anti-insect effect and the ability to alter the soil microbial ecology, making it vital to agriculture. Ultrasound, microwave, supercritical fluid, ionic liquid, and acid hydrolysis extract friedelin with reduced environmental impact. Recently, the high demand for friedelin has led to the development of CRISPR/Cas9 technology and gene overexpression plasmids to produce friedelin using genetically engineered yeast. Friedelin with low cytotoxicity to normal cells can be the best phytochemical for the drug of choice. The review summarizes the structural interpretation, biosynthesis, physicochemical properties, quantification, and various forms of pharmacological significance. [ABSTRACT FROM AUTHOR]

Mungbean is known to be susceptible to waterlogging (WL) stress. Some of the wild species have the potential to tolerate this through various physiological and molecular mechanisms. Auxin Response Factor (ARF) and Auxin/Indole Acetic Acid (AUX/IAA), an early responsive gene family, has multiple functions in growth, development, and stress tolerance. Here, we report the first comprehensive analysis of the ARF and AUX/IAA gene family in mungbean. A total of 26 ARF and 19 AUX/IAA genes were identified from the mungbean genome. The ARF and AUX/IAA candidates were clearly grouped into two major clades. Further, the subgrouping within the major clades indicated the presence of significant diversity. The gene structure, motif analysis, and protein characterization provided the clue for further fundamental research. Out of the10 selected candidate genes, VrARF-5, VrARF-11, VrARF-25, and VrAUX/IAA-9 were found to significantly multiple-fold gene expression in the hypocotyl region of WL-tolerant wild relatives (PRR 2008-2) provides new insight into a role in the induction of lateral root formation under WL stress. The analysis provides an insight into the structural diversity of ARF and AUX/IAA genes in mungbean. These results increase our understanding of ARF and AUX/IAA genes and therefore offer robust information for functional investigations, which can be taken up in the future and will form a foundation for improving tolerance against waterlogging stress. [ABSTRACT FROM AUTHOR]

The development of multidrug resistance (MDR) against chemotherapeutic agents has become a major impediment in cancer therapy. Understanding the underlying mechanism behind MDR can guide future treatment for cancer with better therapeutic outcomes. Recent studies evidenced that crossroads interaction between the heat shock proteins (HSP) and inflammatory responses under the tumor microenvironment plays a pivotal role in modulating drug responsiveness and drug resistance through a complex cytological process. This review aims to investigate the interrelationship between inflammation and HSP in acquiring multiple drug resistance and investigate strategies to overcome the drug resistance to improve the efficacy of cancer treatment. HSP plays a dual regulatory effect as an immunosuppressive and immunostimulatory agent, involving the simultaneous blockade of multiple signaling pathways in acquiring MDR. For example, HSP27 shows biological effects on monocytes by causing IL10 and TNFα secretion and blocking monocyte differentiation to normal dendritic cells and tumor-associated macrophages to promote cancer progression and chemoresistance. Thus, the HSP function and immune-checkpoint release modalities provide a therapeutic target for a therapeutically beneficial approach for enhancing anti-tumor immune responses. The interconnection between inflammation and HSP, along with the tumor microenvironment in acquiring drug resistance, has become crucial for rationalizing the effect of HSP immunomodulatory activity with immune checkpoint blockade. This relationship can overcome drug resistance and assist in the development of novel combinatorial cancer immunotherapy in fighting cancer with decreasing mortality rates. [ABSTRACT FROM AUTHOR]

The rising predominance of type 2 diabetes, combined with the poor medical effects seen with commercially available anti-diabetic medications, has motivated the development of innovative treatment approaches for regulating postprandial glucose levels. Natural carbohydrate digestion enzyme inhibitors might be a viable option for blocking dietary carbohydrate absorption with fewer side effects than manufactured medicines. Alpha-amylase is a metalloenzyme that facilitates digestion by breaking down polysaccharides into smaller molecules such as maltose and maltotriose. It also contributes to elevated blood glucose levels and postprandial hyperglycemia. As a result, scientists are being urged to target α-amylase and create inhibitors that can slow down the release of glucose from carbohydrate chains and prolong its absorption, thereby resulting in lower postprandial plasma glucose levels. Natural α-amylase inhibitors derived from plants have gained popularity as safe and cost-effective alternatives. The bioactive components responsible for the inhibitory actions of various plant extracts have been identified through phytochemical research, paving the way for further development and application. The majority of the findings, however, are based on in vitro investigations. Only a few animal experiments and very few human investigations have confirmed these findings. Despite some promising results, additional investigation is needed to develop feasible anti-diabetic drugs based on plant-derived pancreatic α-amylase inhibitors. This review summarizes the most recent findings from research on plant-derived pancreatic α-amylase inhibitors, including plant extracts and plant-derived bioactive compounds. Furthermore, it offers insights into the structural aspects of the crucial therapeutic target, α-amylases, in addition to their interactions with inhibitors. [ABSTRACT FROM AUTHOR]

Biological control of plant diseases has gained attraction for controlling various bacterial diseases at a field trial stage. An isolated endophytic bacterium, Bacillus velezensis 25 (Bv-25), from Citrus species had strong antagonistic activity against Xanthomonas citri subsp. citri (Xcc), which causes citrus canker disease. When Bv-25 was incubated in Landy broth or yeast nutrient broth (YNB), the ethyl acetate extract of Landy broth exhibited higher levels of antagonistic activity against Xcc compared to that of YNB. Therefore, the antimicrobial compounds in the two ethyl acetate extracts were detected by high performance liquid chromatography–mass spectrometry. This comparison revealed an increase in production of several antimicrobial compounds, including difficidin, surfactin, fengycin, and Iturin-A or bacillomycin-D by incubation in Landy broth. RNA sequencing for the Bv-25 grown in Landy broth were performed, and the differential expressions were detected for the genes encoding the enzymes for the synthesis of antimicrobial compounds, such as bacilysin, plipastatin or fengycin, surfactin, and mycosubtilin. Combination of metabolomics analysis and RNA sequencing strongly suggests that several antagonistic compounds, especially bacilysin produced by B. velezensis, exhibit an antagonistic effect against Xcc. [ABSTRACT FROM AUTHOR]

The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction. [ABSTRACT FROM AUTHOR]

Alkaloids are the most diversified nitrogen-containing secondary metabolites, having antioxidant and antimicrobial properties, and are extensively used in pharmaceuticals to treat different types of cancer. Nicotiana serves as a reservoir of anti-cancer alkaloids and is also used as a model plant for the de novo synthesis of various anti-cancer molecules through genetic engineering. Up to 4% of the total dry weight of Nicotiana was found to be composed of alkaloids, where nicotine, nornicotine, anatabine, and anabasine are reported as the dominant alkaloids. Additionally, among the alkaloids present in Nicotiana, β-carboline (Harmane and Norharmane) and Kynurenines are found to show anti-tumor effects, especially in the cases of colon and breast cancers. Creating new or shunting of existing biosynthesis pathways in different species of Nicotiana resulted in de novo or increased synthesis of different anti-tumor molecules or their derivatives or precursors including Taxadiane (~22.5 µg/g), Artemisinin (~120 μg/g), Parthenolide (~2.05 ng/g), Costunolide (~60 ng/g), Etoposide (~1 mg/g), Crocin (~400 µg/g), Catharanthine (~60 ng/g), Tabersonine (~10 ng/g), Strictosidine (~0.23 mg/g), etc. Enriching the precursor pool, especially Dimethylallyl Diphosphate (DMAPP), down-regulating other bi-product pathways, compartmentalization or metabolic shunting, or organelle-specific reconstitution of the precursor pool, might trigger the enhanced accumulation of the targeted anti-cancer alkaloid in Nicotiana. [ABSTRACT FROM AUTHOR]

In ovarian cancer patients, the 5-year survival rate is 90% for stages I and II, but only 30% for stages III and IV. Unfortunately, as 75% of the patients are diagnosed at stages III and IV, many experience a recurrence. To ameliorate this, it is necessary to develop new biomarkers for early diagnosis and treatment. The ubiquitin–proteasome system is a post-translational modification that plays an important role in regulating protein stability through ubiquitination. In particular, deubiquitinating enzymes (DUBs) regulate protein stability through deubiquitinating substrate proteins. In this review, DUBs and substrates regulated by these enzymes are summarized based on their functions in ovarian cancer cells. This would be useful for the discovery of biomarkers for ovarian cancer and developing new therapeutic candidates. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a complex illness in which the body does not create enough insulin to control blood glucose levels. Worldwide, this disease is life-threatening and requires low-cost, side-effect-free medicine. Due to adverse effects, many synthetic hypoglycemic medications for diabetes fail. Mushrooms are known to contain natural bioactive components that may be anti-diabetic; thus, scientists are now targeting them. Mushroom extracts, which improve immune function and fight cancer, are becoming more popular. Mushroom-derived functional foods and dietary supplements can delay the onset of potentially fatal diseases and help treat pre-existing conditions, which leads to the successful prevention and treatment of type 2 diabetes, which is restricted to the breakdown of complex polysaccharides by pancreatic-amylase and the suppression of intestinal-glucosidase. Many mushroom species are particularly helpful in lowering blood glucose levels and alleviating diabetes symptoms. Hypoglycaemic effects have been observed in investigations on Agaricussu brufescens, Agaricus bisporus, Cordyceps sinensis, Inonotus obliqus, Coprinus comatus, Ganoderma lucidum, Phellinus linteus, Pleurotus spp., Poria cocos, and Sparassis crispa. For diabetics, edible mushrooms are high in protein, vitamins, and minerals and low in fat and cholesterol. The study found that bioactive metabolites isolated from mushrooms, such as polysaccharides, proteins, dietary fibers, and many pharmacologically active compounds, as well as solvent extracts of mushrooms with unknown metabolites, have anti-diabetic potential in vivo and in vitro, though few are in clinical trials. [ABSTRACT FROM AUTHOR]

Cannabis belongs to the family Cannabaceae, and phytocannabinoids are produced by the Cannabis sativa L. plant. A long-standing debate regarding the plant is whether it contains one or more species. Phytocannabinoids are bioactive natural products found in flowers, seeds, and fruits. They can be beneficial for treating human diseases (such as multiple sclerosis, neurodegenerative diseases, epilepsy, and pain), the cellular metabolic process, and regulating biological function systems. In addition, several phytocannabinoids are used in various therapeutic and pharmaceutical applications. This study provides an overview of the different sources of phytocannabinoids; further, the biosynthesis of bioactive compounds involving various pathways is elucidated. The structural classification of phytocannabinoids is based on their decorated resorcinol core and the bioactivities of naturally occurring cannabinoids. Furthermore, phytocannabinoids have been studied in terms of their role in animal models and antimicrobial activity against bacteria and fungi; further, they show potential for therapeutic applications and are used in treating various human diseases. Overall, this review can help deepen the current understanding of the role of biotechnological approaches and the importance of phytocannabinoids in different industrial applications. [ABSTRACT FROM AUTHOR]

Microbial biocontrol agents are efficient and environment-friendly in eradicating plant pathogenic bacteria. In recent years, Bacillus velezensis has gained popularity as a potential biocontrol agent in many countries. Several B. velezensis-based biocontrol products, previously identified as B. amyloliquefaciens or B. amyloliquefaciens subsp. plantarum, have received commercial approval, particularly in China and Europe. In this study, we compiled recent research findings on B. velezensis related to the production of antimicrobials, volatile organic compounds, induction of disease resistance, and the effect of this bacterium on plant growth promotion and yield. However, some recent research indicates that this important resource is also linked to several diseases in crops, including peach, onion, and potato, and the negative aspects of this bacterium in terms of its virulence traits to infect crops have not been summarized before. In this review, we compile the recent reports of this bacterium in term of its beneficial properties in agriculture. In addition, we also discuss several reports about its harmful effect on several crops as well. Therefore, due to the inherent pathogenicity of this bacterium to several crops, care must be taken when using it in a novel crop cultivation technique. [ABSTRACT FROM AUTHOR]

Cancer is one of the most dangerous health problems in the millennium and it is the third foremost human cause of death in the universe. Traditional cancer treatments face several disadvantages and cannot often afford adequate outcomes. It has been exhibited that the outcome of several therapies can be improved when associated with nanostructures. In addition, a modern tendency is being developed in cancer therapy to convert single-modal into multi-modal therapies with the help of existing various nanostructures. Among them, gold is the most successful nanostructure for biomedical applications due to its flexibility in preparation, stabilization, surface modifications, less cytotoxicity, and ease of bio-detection. In the past few decades, gold-based nanomaterials rule cancer treatment applications, currently, gold nanostructures were the leading nanomaterials for synergetic cancer therapies. In this review article, the synthesis, stabilization, and optical properties of gold nanostructures have been discussed. Then, the surface modifications and targeting mechanisms of gold nanomaterials will be described. Recent signs of progress in the application of gold nanomaterials for synergetic cancer therapies such as photodynamic and photo-thermal therapies in combination with other common interventions such as radiotherapy, chemotherapy, and will be reviewed. Also, a summary of the pharmacokinetics of gold nanostructures will be delivered. Finally, the challenges and outlooks of the gold nanostructures in the clinics for applications in cancer treatments are debated. [ABSTRACT FROM AUTHOR]

The world is facing a global financial loss and health effects due to food quality adulteration and contamination, which are seriously affecting human health. Synthetic colors, flavors, and preservatives are added to make food more attractive to consumers. Therefore, food safety has become one of the fundamental needs of mankind. Due to the importance of food safety, the world is in great need of developing desirable and accurate methods for determining the quality of food. In recent years, the electrochemical methods have become more popular, due to their simplicity, ease in handling, economics, and specificity in determining food safety. Common food contaminants, such as pesticides, additives, and animal drug residues, cause foods that are most vulnerable to contamination to undergo evaluation frequently. The present review article discusses the electrochemical detection of the above food contaminants using different carbon nanomaterials, such as carbon nanotubes (CNTs), graphene, ordered mesoporous carbon (OMC), carbon dots, boron doped diamond (BDD), and fullerenes. The voltammetric methods, such as cyclic voltammetry (CV) and differential pulse voltammetry (DPV), have been proven to be potential methods for determining food contaminants. The use of carbon-based electrodes has the added advantage of electrochemically sensing the food contaminants due to their excellent sensitivity, specificity, large surface area, high porosity, antifouling, and biocompatibility. [ABSTRACT FROM AUTHOR]

Citrus is one of the main fruit crops cultivated in tropical and subtropical regions worldwide. Approximately half (40–47%) of the fruit mass is inedible and discarded as waste after processing, which causes pollution to the environment. Essential oils (EOs) are aromatic compounds found in significant quantities in oil sacs or oil glands present in the leaves, flowers, and fruit peels (mainly the flavedo part). Citrus EO is a complex mixture of ~400 compounds and has been found to be useful in aromatic infusions for personal health care, perfumes, pharmaceuticals, color enhancers in foods and beverages, and aromatherapy. The citrus EOs possess a pleasant scent, and impart relaxing, calming, mood-uplifting, and cheer-enhancing effects. In aromatherapy, it is applied either in message oils or in diffusion sprays for homes and vehicle sittings. The diffusion creates a fresh feeling and enhances relaxation from stress and anxiety and helps uplifting mood and boosting emotional and physical energy. This review presents a comprehensive outlook on the composition, properties, characterization, and mechanism of action of the citrus EOs in various health-related issues, with a focus on its antioxidant properties. [ABSTRACT FROM AUTHOR]

The development of functional neural circuits in the central nervous system (CNS) requires the production of sufficient numbers of various types of neurons and glial cells, such as astrocytes and oligodendrocytes, at the appropriate periods and regions. Hence, severe neuronal loss of the circuits can cause neurodegenerative diseases such as Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Treatment of such neurodegenerative diseases caused by neuronal loss includes some strategies of cell therapy employing stem cells (such as neural progenitor cells (NPCs)) and gene therapy through cell fate conversion. In this report, we review how bHLH acts as a regulator in neuronal differentiation, reprogramming, and cell fate determination. Moreover, several different researchers are conducting studies to determine the importance of bHLH factors to direct neuronal and glial cell fate specification and differentiation. Therefore, we also investigated the limitations and future directions of conversion or transdifferentiation using bHLH factors. [ABSTRACT FROM AUTHOR]

The Bax protein is a pro-apoptotic protein belonging to the Bcl-2 family, involved in inducing apoptosis at the mitochondrial level. Regulating the protein levels of Bax is essential to enhancing apoptosis. In the current study, we ascertained the presence of deubiquitinating enzymes (DUBs) associated with Bax by performing the yeast two-hybrid screening (Y2H). We determined that ubiquitin-specific protease 12 (USP12), one of the DUBs, is associated with Bax. The binding of USP12 to Bax shows the interaction as a DUB, which regulates ubiquitination on Bax. Taken together, we believe that USP12 regulates Bax by detaching ubiquitin on K63-linked chains, indicating that USP12 affects the cellular functions of Bax, but it is not related with proteasomal degradation. The half-life of the Bax protein was determined by performing the site-directed mutagenesis of putative ubiquitination sites on Bax (K128R, K189R, and K190R). Of these, Bax (K128R and K190R) showed less ubiquitination; therefore, we compared the half-life of Bax (WT) and Bax K mutant forms in vitro. Interestingly, Bax (K189R) showed a higher ubiquitination level and shorter half-life than Bax (WT), and the (K128R and K190R) mutant form has a longer half-life than Bax (WT). [ABSTRACT FROM AUTHOR]

Diabetes is a common metabolic disorder marked by unusually high plasma glucose levels, which can lead to serious consequences such as retinopathy, diabetic neuropathy and cardiovascular disease. One of the most efficient ways to reduce postprandial hyperglycemia (PPHG) in diabetes mellitus, especially insulin-independent diabetes mellitus, is to lower the amount of glucose that is absorbed by inhibiting carbohydrate hydrolyzing enzymes in the digestive system, such as α-glucosidase and α-amylase. α-Glucosidase is a crucial enzyme that catalyzes the final stage of carbohydrate digestion. As a result, α-glucosidase inhibitors can slow D-glucose release from complex carbohydrates and delay glucose absorption, resulting in lower postprandial plasma glucose levels and control of PPHG. Many attempts have been made in recent years to uncover efficient α-glucosidase inhibitors from natural sources to build a physiologic functional diet or lead compound for diabetes treatment. Many phytoconstituent α-glucosidase inhibitors have been identified from plants, including alkaloids, flavonoids, anthocyanins, terpenoids, phenolic compounds, glycosides and others. The current review focuses on the most recent updates on different traditional/medicinal plant extracts and isolated compounds' biological activity that can help in the development of potent therapeutic medications with greater efficacy and safety for the treatment of type 2 diabetes or to avoid PPHG. For this purpose, we provide a summary of the latest scientific literature findings on plant extracts as well as plant-derived bioactive compounds as potential α-glucosidase inhibitors with hypoglycemic effects. Moreover, the review elucidates structural insights of the key drug target, α-glucosidase enzymes, and its interaction with different inhibitors. [ABSTRACT FROM AUTHOR]

The widespread use of fertilizers is a result of the increased global demand for food. The commonly used chemical fertilizers may increase plant growth and output, but they have deleterious effects on the soil, the environment, and even human health. Therefore, nanofertilizers are one of the most promising solutions or substitutes for conventional fertilizers. These engineered materials are composed of nanoparticles containing macro- and micronutrients that are delivered to the plant rhizosphere in a regulated manner. In nanofertilizers, the essential minerals and nutrients (such as N, P, K, Fe, and Mn) are bonded alone or in combination with nano-dimensional adsorbents. This review discusses the development of nanotechnology-based smart and efficient agriculture using nanofertilizers that have higher nutritional management, owing to their ability to increase the nutrient uptake efficiency. Additionally, the synthesis and mechanism of action of the nanofertilizers are discussed, along with the different types of fertilizers that are currently available. Furthermore, sustainable agriculture can be realised by the targeted delivery and controlled release of nutrients through the application of nanoscale active substances. This paper emphasises the successful development and safe application of nanotechnology in agriculture; however, certain basic concerns and existing gaps in research need to be addressed and resolved. [ABSTRACT FROM AUTHOR]

Carbon nanodots (CNDs) are advanced nanomaterials with a size of 2–10 nm and are considered zero-dimensional carbonaceous materials. CNDs have received great attention in the area of cancer theranostics. The majority of review articles have shown the improvement of CNDs for use in cancer therapy and bioimaging applications. However, there is a minimal number of consolidated studies on the currently developed doped CNDs that are used in various ways in cancer therapies. Hence, in this review, we discuss the current developments in different types of heteroatom elements/metal ion-doped CNDs along with their preparations, physicochemical and biological properties, multimodal-imaging, and emerging applications in image-guided photodynamic therapies for cancer. [ABSTRACT FROM AUTHOR]

Despite the discovery and development of an array of antimicrobial agents, multidrug resistance poses a major threat to public health and progressively increases mortality. Recently, several studies have focused on developing promising solutions to overcome these problems. This has led to the development of effective alternative methods of controlling antibiotic-resistant pathogens. The use of antimicrobial agents in combination can produce synergistic effects if each drug invades a different target or signaling pathway with a different mechanism of action. Therefore, drug combinations can achieve a higher probability and selectivity of therapeutic responses than single drugs. In this systematic review, we discuss the combined effects of different antimicrobial agents, such as plant extracts, essential oils, and nanomaterials. Furthermore, we review their synergistic interactions and antimicrobial activities with the mechanism of action, toxicity, and future directions of different antimicrobial agents in combination. Upon combination at an optimum synergistic ratio, two or more drugs can have a significantly enhanced therapeutic effect at lower concentrations. Hence, using drug combinations could be a new, simple, and effective alternative to solve the problem of antibiotic resistance and reduce susceptibility. [ABSTRACT FROM AUTHOR]

The CDC73/HRPT2 gene, a defect which causes hyperparathyroidism–jaw tumor (HPT-JT) syndrome, encodes CDC73/parafibromin. We aimed to investigate whether CDC73 would be a target for ubiquitin–proteasome degradation. We cloned full-length cDNAs encoding a family of 58 ubiquitin-specific deubiquitinating enzymes (DUBs), also known as ubiquitin-specific proteases (USPs). Use of the yeast two-hybrid system then enabled us to identify USP37 as interacting with CDC73. The biochemical interaction between the USP37 and CDC73 and their reciprocal binding domains were studied. Co-localization of CDC73 and USP37 was observed in cells. CDC73 was found to be polyubiquitinated, and polyubiquitination of CDC73 was prominent in mutants. CDC73 was deubiquitinated via K48-specific ubiquitin chains by USP37, but not by the catalytically inactive USP37C350S mutant. Observation of the binding between deletion mutants of CDC73 and USP37 revealed that the β-catenin binding site of CDC73 and the ubiquitin-interacting motifs 2 and 3 (UIM2 and 3) of USP37 were responsible for the interaction between the two proteins. Moreover, these two enzymes co-existed within the nucleus of COS7 cells. We conclude that USP37 is a DUB for CDC73 and that the two proteins interact through specific domains, suggesting that USP37 is responsible for the stability of CDC73 in HPT-JT syndrome. [ABSTRACT FROM AUTHOR]

Microbes produce a diverse range of secondary metabolites in response to various environmental factors and interspecies competition. This enables them to become superior in a particular environment. Bacilysin, a dipeptide antibiotic produced by Bacillus species, is active against a broad range of microorganisms. Because of its simple structure and excellent mode of action, i.e., through the inhibition of glucosamine 6-phosphate synthase, it has drawn the attention of researchers. In addition, it acts as a pleiotropic signaling molecule that affects different cellular activities. However, all Bacillus species are not capable of producing bacilysin. The biosynthesis of bacilysin by Bacillus species is not uniform throughout the population; specificity and heterogeneity at both the strain and species levels has been observed. This review discusses how bacilysin is biosynthesized by Bacillus species, the regulators of its biosynthesis, its importance in the host, and the abiotic factors affecting bacilysin production. [ABSTRACT FROM AUTHOR]

Mushrooms have remained an eternal part of traditional cuisines due to their beneficial health potential and have long been recognized as a folk medicine for their broad spectrum of nutraceuticals, as well as therapeutic and prophylactic uses. Nowadays, they have been extensively investigated to explain the chemical nature and mechanisms of action of their biomedicine and nutraceuticals capacity. Mushrooms belong to the astounding dominion of Fungi and are known as a macrofungus. Significant health benefits of mushrooms, including antiviral, antibacterial, antiparasitic, antifungal, wound healing, anticancer, immunomodulating, antioxidant, radical scavenging, detoxification, hepatoprotective cardiovascular, anti-hypercholesterolemia, and anti-diabetic effects, etc., have been reported around the globe and have attracted significant interests of its further exploration in commercial sectors. They can function as functional foods, help in the treatment and therapeutic interventions of sub-optimal health states, and prevent some consequences of lifethreatening diseases. Mushrooms mainly contained low and high molecular weight polysaccharides, fatty acids, lectins, and glucans responsible for their therapeutic action. Due to the large varieties of mushrooms present, it becomes challenging to identify chemical components present in them and their beneficial action. This article highlights such therapeutic activities with their active ingredients for mushrooms. [ABSTRACT FROM AUTHOR]

Foodborne illness and disease caused by foodborne pathogenic bacteria is continuing to increase day by day and it has become an important topic of concern among various food industries. Many types of synthetic antibacterial agents have been used in food processing and food preservation; however, they are not safe and have resulted in various health-related issues. Therefore, in the present study, essential oil from an edible seaweed, Enteromorpha linza (AEO), was evaluated for its antibacterial activity against foodborne pathogens, along with the mechanism of its antibacterial action. AEO at 25 mg/disc was highly active against Bacillus cereus (12.3–12.7 mm inhibition zone) and Staphylococcus aureus (12.7–13.3 mm inhibition zone). The minimum inhibitory concentration and minimum bactericidal concentration values of AEO ranged from 12.5–25 mg/mL. Further investigation of the mechanism of action of AEO revealed its strong impairing effect on the viability of bacterial cells and membrane permeability, as indicated by a significant increase in leakage of 260 nm absorbing materials and K+ ions from the cell membrane and loss of high salt tolerance. Taken together, these data suggest that AEO has the potential for use as an effective antibacterial agent that functions by impairing cell membrane permeability via morphological alternations, resulting in cellular lysis and cell death. [ABSTRACT FROM AUTHOR]

Recent healthcare systems based on human body communication (HBC) require human interaction sensors. Due to the conductive properties of the human body, capacitive sensors are most widely known and are applied to many electronic gadgets for communication. Capacitance fluctuations due to the fact of human interaction are typically converted to voltage levels using some analog circuits, and then analog-to-digital converters (ADCs) are used to convert analog voltages into digital codes for further processing. However, signals detected by human touch naturally contain large noise, and an active analog filter that consumes a lot of power is required. In addition, the inclusion of ADCs causes the system to use a large area and amount of power. The proposed structure adopts a digital-based moving average filter (MAF) that can effectively operate as a low-pass filter (LPF) instead of a large-area and high-power consumption analog filter. In addition, the proposed ∆C detection algorithm can distinguish between human interaction and object interaction. As a result, two individual digital signals of touch/release and movement can be generated, and the type and strength of the touch can be effectively expressed without the help of an ADC. The prototype chip of the proposed capacitive sensing circuit was fabricated with commercial 65 nm CMOS process technology, and its functionality was fully verified through testing and measurement. The prototype core occupies an active area of 0.0067 mm2, consumes 7.5 uW of power, and has a conversion time of 105 ms. [ABSTRACT FROM AUTHOR]

Distance computation between two input vectors is a widely used computing unit in several pattern recognition, signal processing and neuromorphic applications. However, the implementation of such a functionality in conventional CMOS design requires expensive hardware and involves significant power consumption. Even power-efficient current-mode analog designs have proved to be slower and vulnerable to variations. In this paper, we propose an approximate mixed-signal design for the distance computing core by noting the fact that a vast majority of the signal processing applications involving this operation are resilient to small approximations in the distance computation. The proposed mixed-signal design is able to interface with external digital CMOS logic and simultaneously exhibit fast operating speeds. Another important feature of the proposed design is that the computing core is able to compute two variants of the distance metric, namely the (i) Euclidean distance squared ( L 2 2 norm) and (ii) Manhattan distance ( L 1 norm). The performance of the proposed design was evaluated on a standard K-means clustering algorithm on the "Iris flower dataset". The results indicate a throughput of 6 ns per classification and ∼2.3× lower energy consumption in comparison to a synthesized digital CMOS design in commercial 45 nm CMOS technology. [ABSTRACT FROM AUTHOR]

A hybrid control method using a comparator and a charge control method is proposed for a single-inductor multiple-output (SIMO) DC-DC converter. SIMO DC-DC converters have the weaknesses relating to cross-regulation, as all the output channels share the energy stored in a single inductor. Although multiple control methods such as Time-Multiplexing Control (TMC) and Ordered Power Distributing Control (OPDC) have been proposed to prevent cross-regulation or to improve load capability, effective use of limited resources appears to have not yet been achieved. This paper introduces a hybrid control topology that (1) utilizes comparator-based regulations for most outputs and (2) uses a new charge control loop method for the last output to reduce cross-regulation with low hardware complexity. In addition, the proposed scheme efficiently reuses the system's redundant energy by adaptively controlling the freewheeling switch that opens the path to the input battery to store the surplus energy resources again. The proposed SIMO DC-DC converter was designed and validated with a 0.18 μm 3.3 V CMOS process. The converter has four regulated outputs of 0.9, 1.2, 1.5, and 2.2 V, and as a result of the simulation, it was found that the cross-regulation was estimated to be 0.4 mV/mA when the output current changes by ~200 mA. In addition, estimated peak power conversion efficiency of 88.5% was achieved at a total output power of 405 mW. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML), the most common form of an acute leukemia, is a malignant disorder of stem cell precursors of the myeloid lineage. Ubiquitination is one of the post-translational modifications (PTMs), and the ubiquitin-like proteins (Ubls; SUMO, NEDD8, and ISG15) play a critical role in various cellular processes, including autophagy, cell-cycle control, DNA repair, signal transduction, and transcription. Also, the importance of Ubls in AML is increasing, with the growing research defining the effect of Ubls in AML. Numerous studies have actively reported that AML-related mutated proteins are linked to Ub and Ubls. The current review discusses the roles of proteins associated with protein ubiquitination, modifications by Ubls in AML, and substrates that can be applied for therapeutic targets in AML. [ABSTRACT FROM AUTHOR]

Perishable food spoilage caused by fungi is a major cause of discomfort for food producers. Food sensory abnormalities range from aesthetic degeneration to significant aroma, color, or consistency alterations due to this spoilage. Bio-preservation is the use of natural or controlled bacteria or antimicrobials to enhance the quality and safety of food. It has the ability to harmonize and rationalize the required safety requirements with conventional preservation methods and food production safety and quality demands. Even though synthetic preservatives could fix such issues, there is indeed a significant social need for "clean label" foods. As a result, consumers are now seeking foods that are healthier, less processed, and safer. The implementation of antifungal compounds has gotten a lot of attention in recent decades. As a result, the identification and characterization of such antifungal agents has made promising advances. The present state of information on antifungal molecules, their modes of activity, connections with specific target fungi varieties, and uses in food production systems are summarized in this review. [ABSTRACT FROM AUTHOR]

Polymeric nanocomposites have received significant attention in both scientific and industrial research in recent years. The demand for new methods of food preservation to ensure high-quality, healthy foods with an extended shelf life has increased. Packaging, a crucial feature of the food industry, plays a vital role in satisfying this demand. Polymeric nanocomposites exhibit remarkably improved packaging properties, including barrier properties, oxygen impermeability, solvent resistance, moisture permeability, thermal stability, and antimicrobial characteristics. Bio-based polymers have drawn considerable interest to mitigate the influence and application of petroleum-derived polymeric materials and related environmental concerns. The integration of nanotechnology in food packaging systems has shown promise for enhancing the quality and shelf life of food. This article provides a general overview of bio-based polymeric nanocomposites comprising polymer matrices and inorganic nanoparticles, and describes their classification, fabrication, properties, and applications for active food packaging systems with future perspectives. [ABSTRACT FROM AUTHOR]

A stomatal pore is formed by a pair of specialized guard cells and serves as a major gateway for water transpiration and atmospheric CO2 influx for photosynthesis in plants. These pores must be tightly controlled, as inadequate CO2 intake and excessive water loss are devastating for plants. When the plants are exposed to extreme weather conditions such as high CO2 levels, O3, low air humidity, and drought, the turgor pressure of the guard cells exhibits an appropriate response against these stresses, which leads to stomatal closure. This phenomenon involves a complex network of ion channels and their regulation. It is well-established that the turgor pressure of guard cells is regulated by ions transportation across the membrane, such as anions and potassium ions. In this review, the guard cell ion channels are discussed, highlighting the structure and functions of key ion channels; the SLAC1 anion channel and KAT1 potassium channel, and their regulatory components, emphasizing their significance in guard cell response to various stimuli. [ABSTRACT FROM AUTHOR]

Free radicals are generated as byproducts of normal metabolic processes as well as due to exposure to several environmental pollutants. They are highly reactive species, causing cellular damage and are associated with a plethora of oxidative stress-related diseases and disorders. Antioxidants can control autoxidation by interfering with free radical propagation or inhibiting free radical formation, reducing oxidative stress, improving immune function, and increasing health longevity. Antioxidant functionalized metal nanoparticles, transition metal oxides, and nanocomposites have been identified as potent nanoantioxidants. They can be formulated in monometallic, bimetallic, and multi-metallic combinations via chemical and green synthesis techniques. The intrinsic antioxidant properties of nanomaterials are dependent on their tunable configuration, physico-chemical properties, crystallinity, surface charge, particle size, surface-to-volume ratio, and surface coating. Nanoantioxidants have several advantages over conventional antioxidants, involving increased bioavailability, controlled release, and targeted delivery to the site of action. This review emphasizes the most pioneering types of nanoantioxidants such as nanoceria, silica nanoparticles, polydopamine nanoparticles, and nanocomposite-, polysaccharide-, and protein-based nanoantioxidants. This review overviews the antioxidant potential of biologically synthesized nanomaterials, which have emerged as significant alternatives due to their biocompatibility and high stability. The promising nanoencapsulation nanosystems such as solid lipid nanoparticles, nanostructured lipid carriers, and liposome nanoparticles are highlighted. The advantages, limitations, and future insights of nanoantioxidant applications are discussed. [ABSTRACT FROM AUTHOR]

Sampling-based PLLs have become a new research trend due to the possibility of removing the frequency divider (FDIV) from the feedback path, where the FDIV increases the contribution of in-band noise by the factor of dividing ratio square (N2). Between two possible sampling methods, sub-sampling and reference-sampling, the latter provides a relatively wide locking range, as the slower input reference signal is sampled with the faster VCO output signal. However, removal of FDIV makes the PLL not feasible to implement fractional-N operation based on varying divider ratios through random sequence generators, such as a Delta-Sigma-Modulator (DSM). To address the above design challenges, we propose a reference-sampling-based calibration-free fractional-N PLL (RSFPLL) with a phase-interpolator-linked sampling clock generator (PSCG). The proposed RSFPLL achieves fractional-N operations through phase-interpolator (PI)-based multi-phase generation instead of a typical frequency divider or digital-to-time converter (DTC). In addition, to alleviate the power burden arising from VCO-rated sampling, a flexible mask window generation method has been used that only passes a few sampling clocks near the point of interest. The prototype PLL system is designed with a 65 nm CMOS process with a chip size of 0.42 mm2. It achieves 322 fs rms jitter, −240.7 dB figure-of-merit (FoM), and −44.06 dBc fractional spurs with 8.17 mW power consumption. [ABSTRACT FROM AUTHOR]

The development of food-borne and infectious diseases has increased globally at an anomalous rate and is combined with emerging social and economic problems. This highlights the need for new and improved antibacterial agents with novel and different mechanisms of action at regular intervals. Some chemical or artificial food additives are considered harmful if they are used beyond their permissible levels. Today, consumers are demanding alternative, green, safer, and natural food additives to increase the shelf life of food. Essential oils (EOs) are concentrated liquid mixtures of volatile compounds with antioxidant and antibacterial properties that can be used as natural, eco-friendly, renewable, and cost-effective additives. The use of combinations of different EOs and their components is a promising strategy to increase the synergistic and additive effects of EOs in foods. In this article, we review the recent literature on EOs concerning the chemical constituents, extraction methods, antioxidant and antibacterial activities, and their mechanisms of action. Additionally, we discuss the synergistic interaction of different EOs and their components, challenges, and future directions of EOs as natural food preservatives, with special emphasis on shelf life extension and applications in the packaging of food products. [ABSTRACT FROM AUTHOR]

When functioning properly, the stomach is the center of both physical and mental satisfaction. Gastrointestinal disorders, or malfunctioning of the stomach, due to infections caused by various biological entities and physiochemical abnormalities, are now widespread, with most of the diseases being inflammatory, which, depending on the position and degree of inflammation, have different names such as peptic or gastric ulcers, irritable bowel diseases, ulcerative colitis, and so on. While many synthetic drugs, such as non-steroidal anti-inflammatory drugs, are now extensively used to treat these diseases, their harmful and long-term side effects cannot be ignored. To treat these diseases safely and successfully, different potent medicinal plants and their active components are considered game-changers. In consideration of this, the present review aimed to reveal a general and comprehensive updated overview of the anti-ulcer and anti-inflammatory activities of medicinal plants. To emphasize the efficacy of the medicinal plants, various bioactive compounds from the plant extract, their experimental animal models, and clinical trials are depicted. [ABSTRACT FROM AUTHOR]

Cancer is a disorder of cell growth and proliferation, characterized by different metabolic pathways within normal cells. The Warburg effect is a major metabolic process in cancer cells that affects the cellular responses, such as proliferation and apoptosis. Various signaling factors down/upregulate factors of the glycolysis pathway in cancer cells, and these signaling factors are ubiquitinated/deubiquitinated via the ubiquitin–proteasome system (UPS). Depending on the target protein, DUBs act as both an oncoprotein and a tumor suppressor. Since the degradation of tumor suppressors and stabilization of oncoproteins by either negative regulation by E3 ligases or positive regulation of DUBs, respectively, promote tumorigenesis, it is necessary to suppress these DUBs by applying appropriate inhibitors or small molecules. Therefore, we propose that the DUBs and their inhibitors related to the Warburg effect are potential anticancer targets. [ABSTRACT FROM AUTHOR]

To increase the half-life of growth hormones, we proposed its long-lasting regulation through the ubiquitin-proteasome system (UPS). We identified lysine residues (K67, K141, and K166) that are involved in the ubiquitination of human growth hormone (hGH) using ubiquitination site prediction programs to validate the ubiquitination sites, and then substituted these lysine residues with arginine residues. We identified the most effective substituent (K141R) to prevent ubiquitination and named it AUT-hGH. hGH was expressed and purified in the form of hGH-His, and ubiquitination was first verified at sites containing K141 in the blood stream. Through the study, we propose that AUT-hGH with an increased half-life could be used as a long-lasting hGH in the blood stream. [ABSTRACT FROM AUTHOR]

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an "ancient" RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation. [ABSTRACT FROM AUTHOR]

Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of ETS genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Here we discuss the known relationships between ETS proteins and enzymes that determine their ubiquitin status, their integration with other developmental signal transduction pathways and how suppression of ETS protein ubiquitination contributes to the malignant cell phenotype in multiple cancers. [ABSTRACT FROM AUTHOR]

Salicylic acid (SA) is an active secondary metabolite that occurs in bacteria, fungi, and plants. SA and its derivatives (collectively called salicylates) are synthesized from chorismate (derived from shikimate pathway). SA is considered an important phytohormone that regulates various aspects of plant growth, environmental stress, and defense responses against pathogens. Besides plants, a large number of bacterial species, such as Pseudomonas, Bacillus, Azospirillum, Salmonella, Achromobacter, Vibrio, Yersinia, and Mycobacteria, have been reported to synthesize salicylates through the NRPS/PKS biosynthetic gene clusters. This bacterial salicylate production is often linked to the biosynthesis of small ferric-ion-chelating molecules, salicyl-derived siderophores (known as catecholate) under iron-limited conditions. Although bacteria possess entirely different biosynthetic pathways from plants, they share one common biosynthetic enzyme, isochorismate synthase, which converts chorismate to isochorismate, a common precursor for synthesizing SA. Additionally, SA in plants and bacteria can undergo several modifications to carry out their specific functions. In this review, we will systematically focus on the plant and bacterial salicylate biosynthesis and its metabolism. [ABSTRACT FROM AUTHOR]

The human genome contains nearly 100 deubiquitinating enzymes (DUBs) responsible for removing ubiquitin moieties from a large variety of substrates. Which DUBs are responsible for targeting which substrates remain mostly unknown. Here we implement the bioUb approach to identify DUB substrates in a systematic manner, combining gene silencing and proteomics analyses. Silencing of individual DUB enzymes is used to reduce their ubiquitin deconjugating activity, leading to an increase of the ubiquitination of their substrates, which can then be isolated and identified. We report here quantitative proteomic data of the putative substrates of 5 human DUBs. Furthermore, we have built a novel interactive database of DUB substrates to provide easy access to our data and collect DUB proteome data from other groups as a reference resource in the DUB substrates research field. [ABSTRACT FROM AUTHOR]

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Even though several basic previous studies have uncovered the versatile roles of USP15 in different signaling networks, those have not yet been systematically and specifically reviewed, which can provide important information about possible disease markers and clinical applications. This review will provide a comprehensive overview of our current understanding of the regulatory mechanisms of USP15 on different signaling pathways for which dynamic reverse ubiquitination is a key regulator. [ABSTRACT FROM AUTHOR]

The ubiquitin (Ub) proteasome system (UPS) plays a pivotal role in regulation of numerous cellular processes, including innate and adaptive immune responses that are essential for restriction of the virus life cycle in the infected cells. Deubiquitination by the deubiquitinating enzyme, deubiquitinase (DUB), is a reversible molecular process to remove Ub or Ub chains from the target proteins. Deubiquitination is an integral strategy within the UPS in regulating survival and proliferation of the infecting virus and the virus-invaded cells. Many viruses in the infected cells are reported to encode viral DUB, and these vial DUBs actively disrupt cellular Ub-dependent processes to suppress host antiviral immune response, enhancing virus replication and thus proliferation. This review surveys the types of DUBs encoded by different viruses and their molecular processes for how the infecting viruses take advantage of the DUB system to evade the host immune response and expedite their replication. [ABSTRACT FROM AUTHOR]

Protein post-translational modifications (PTMs) play key roles in eukaryotes since they finely regulate numerous mechanisms used to diversify the protein functions and to modulate their signaling networks. Besides, these chemical modifications also take part in the viral hijacking of the host, and also contribute to the cellular response to viral infections. All domains of the human immunodeficiency virus type 1 (HIV-1) Gag precursor of 55-kDa (Pr55Gag), which is the central actor for viral RNA specific recruitment and genome packaging, are post-translationally modified. In this review, we summarize the current knowledge about HIV-1 Pr55Gag PTMs such as myristoylation, phosphorylation, ubiquitination, sumoylation, methylation, and ISGylation in order to figure out how these modifications affect the precursor functions and viral replication. Indeed, in HIV-1, PTMs regulate the precursor trafficking between cell compartments and its anchoring at the plasma membrane, where viral assembly occurs. Interestingly, PTMs also allow Pr55Gag to hijack the cell machinery to achieve viral budding as they drive recognition between viral proteins or cellular components such as the ESCRT machinery. Finally, we will describe and compare PTMs of several other retroviral Gag proteins to give a global overview of their role in the retroviral life cycle. [ABSTRACT FROM AUTHOR]

Lannea egregia (Anacardiaceae) and Emilia sonchifolia (Asteraceae) are plants used in traditional medicine in southwestern Nigeria. The essential oils from the leaves of L. egregia and E. sonchifolia were obtained by hydrodistillation and analyzed by gas chromatography–mass spectrometry. Both essential oils were dominated by sesquiterpenoids. The major components in L. egregia leaf essential oil were α-panasinsen (34.90%), (E)-caryophyllene (12.25%), α-copaene (11.39%), and selina-4,11-diene (9.29%), while E. sonchifolia essential oil was rich in γ-himachalene (25.16%), (E)-caryophyllene (15.72%), and γ-gurjunene (8.58%). The essential oils were screened for antimicrobial activity against a panel of bacteria and fungi and displayed minimum inhibitory concentrations ranging from 156 μg/mL to 625 μg/mL. Based on these results, either L. egregia or E. sonchifolia essential oil may be recommended for exploration as complementary antibacterial or antifungal agents. [ABSTRACT FROM AUTHOR]