Search

The delivery of ultra-high dose rates of radiation, called flash irradiation or flash-RT, has emerged as a new modality of radiotherapy shaking up the paradigm of proportionality of effect and dose whatever the method of delivery of the radiation. The hallmark of flash-RT is healthy tissue sparing from the side effects of radiation without decrease of the antitumor efficiency in animal models. In this review we will define its specificities, the molecular mechanisms underlying the flash effect and the ongoing developments to bring this new modality to patient treatment. [ABSTRACT FROM AUTHOR]

• A concise overview on the isolated bioactive compounds from different Annona plant part. • Annona extracts have been shown to exert significant biological and pharmacological activities of isolated compounds with mechanism of its action. • On the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention. The use of plant derived bioactive substances as a key therapeutic agent to treat various diseases has gained great impetus recently. Annona fruits are currently gaining attention from those who are interested in eating foods that promote health because of its phytochemical composition, whose actions have not before been investigated. A comprehensive search was conducted on scientific databases like Google Scholar, PubMed, Science Direct, Scopus etc to retrieve the relevant literature on Annona species include Annona squamosa, Annona muricata, Annona reticulata, Annona glabra, Annona crassiflora, Annona cherimola, Annona montana, Annona purpurea, Annona senegalensis, Annona dioica and Annona atemoya , their bioactive compounds, biological activity, pharmacology and mechanism from January 2002 to February 2024. According to the available literature data bioactive phytocompound have proven to be a potential alternative to synthetic drugs especially because of their antioxidant, antibacterial and in vitro anticancer properties. This review aims to provide up-to-date information on Annona genus with mode of action on various disease. The literature accessible on this plant species was systematically analysed to extract evidence regarding its phytochemicals, including phenolic, ascorbic acid, fatty acids, essential oils, alkaloids etc. Moreover, the considerable data will be useful for pharmaceutical researchers and other industries looking for up-to-date understandings. Specifically, we provide a concise overview on the isolated bioactive compounds from different Annona part and occurrence of the main classes of compounds as well as on the current preclinical evidence an association between bioactive component intake with a special focus on human chronic disease prevention like neurodegenerative, anti-inflammatory, hyperglycaemic and cancer. Additional investigations are necessary to uncover the underlying mechanisms of its actions and conduct clinical trials to verify its effectiveness and safety in humans. [ABSTRACT FROM AUTHOR]

[Display omitted] • Selective autophagy is characterized by its ability to specifically degrade a certain substrate, rather than causing widespread cell autophagy. • The mechanisms underlying selective autophagy can be broadly dispersed in three steps: designation, targeting and sequestration, and degradation. • Numerous human diseases and their progression are closely linked to aberrant selective autophagy. • Deciphering the molecular mechanisms underlying selective autophagy provides a theoretical framework for treating relevant clinical disorders. • Regulation of selective autophagy by discovering and developing small-molecule agents has great clinical application prospects for the treatment of related diseases. Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar (in yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules or organelles for degradation, a process termed selective autophagy. Recently, accumulating studies have demonstrated that the abnormality of selective autophagy is closely associated with the occurrence and progression of many human diseases, including neurodegenerative diseases, cancers, metabolic diseases, and cardiovascular diseases. This review aims at systematically and comprehensively introducing selective autophagy and its role in various diseases, while unravelling the molecular mechanisms of selective autophagy. By providing a theoretical basis for the development of related small-molecule drugs as well as treating related human diseases, this review seeks to contribute to the understanding of selective autophagy and its therapeutic potential. In this review, we systematically introduce and dissect the major categories of selective autophagy that have been discovered. We also focus on recent advances in understanding the molecular mechanisms underlying both classical and non-classical selective autophagy. Moreover, the current situation of small-molecule drugs targeting different types of selective autophagy is further summarized, providing valuable insights into the discovery of more candidate small-molecule drugs targeting selective autophagy in the future. On the other hand, we also reveal clinically relevant implementations that are potentially related to selective autophagy, such as predictive approaches and treatments tailored to individual patients. [ABSTRACT FROM AUTHOR]

Long-term storage of crop seeds is critical for the conservation of germplasm resources, ensuring food supply, and supporting sustainable production. Rice, as a major food staple, has a substantial stock for consumption and production worldwide. However, its food value and seed viability tend to decline during storage. Understanding the physiological responses and molecular mechanisms of aging tolerance forms the basis for enhancing seed storability in rice. This review outlines the latest progress in influential factors, evaluation methods, and identification indices of seed storability. It also discusses the physiological consequences, molecular mechanisms, and strategies for breeding aging-tolerant rice in detail. Finally, it highlights challenges in seed storability research that require future attention. This review offers a theoretical foundation and research direction for uncovering the mechanisms behind seed storability and breeding aging-tolerant rice. [ABSTRACT FROM AUTHOR]

[Display omitted] • Perturbing O-antigen ligation shortened the resuscitating lag phase. • Higher ATP levels of Δ rfaL VBNC cells promote resuscitation. • ATP consumption during lag phase was highly correlated with resuscitation efficiency. • ATP was utilized to activate the Handler and salvage pathways to synthesize NAD+. • VBNC cells using residual ATP recover metabolic activity, driving cells to exit dormancy. Entry into the viable but nonculturable (VBNC) state is a survival strategy adopted by bacteria to survive harsh environment. Although VBNC cells still have metabolic activity, they lose the ability to form colonies on nonselective culture media. Thus, conventional bacterial detection methods, such as plate counting, are unable to detect the presence of VBNC cells. When the environmental conditions are appropriate, VBNC cells can initiate resuscitation, posing a great risk to the safety of public health. The study of the VBNC resuscitation mechanism could provide new insights into the prevention and control of VBNC resuscitation. Uncovering the molecular mechanism of VBNC cell resuscitation by investigating the role of O-antigen ligase (RfaL) in inhibiting the resuscitation of Escherichia coli O157:H7 in the VBNC state. RfaL was screened and verified as a resuscitation inhibitor of VBNC Escherichia coli O157:H7 by detecting resuscitation curve and time-lapse microscopy. The mechanism of RfaL impacts VBNC E. coli resuscitation was investigated by detecting the single cell ATP content, metabolomic changes, NAD(H) content and new protein biosynthesis of WT and Δ rfaL at different stage of resuscitation. Mutation of rfaL , which encoded an O-antigen ligase, markedly shortened the resuscitating lag phase. Further studies indicated that Δ rfaL VBNC cells contained higher ATP levels, and ATP consumption during the resuscitating lag phase was highly correlated with resuscitation efficiency. Metabolomic analysis revealed that ATP was utilized to activate the Handler and salvage pathways to synthesize NAD+, balancing redox reactions to recover cell activity and promote cell resuscitation. Our findings revealed a strategy employed by VBNC cells for revival, that is, using residual ATP to primarily recover metabolic activity, driving cells to exit dormancy. The synthesis pathway of lipopolysaccharide (LPS) in rfaL null mutant was inhibited and could supply more ATP to synthesis NAD+ and promote resuscitation. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is one of the most serious sequelae of trauma with serious impact worldwide. Studies have suggested an association between PTSD and major depressive disorder (MDD), but the underlying common mechanisms remain unclear. This study aimed to further explore the molecular mechanism between PTSD and MDD via comprehensive bioinformatics analysis. The microarray data of PTSD and MDD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify the co-expressed genes associated with PTSD and MDD. Gene Set Enrichment Analysis (GSEA), enrichment analyses based on Disease Ontology (DO), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed using R software. Then, R software was used for single-sample gene set enrichment analysis (ssGSEA) and immune infiltration analysis on the co-expressed genes in the two datasets., Therefore, a logistic regression model was constructed to predict PTSD and MDD using the R language. Ultimately, this study employed PTSD and MDD models to assess alterations in the expression of target genes within the mouse hippocampus. Four core genes (GNAQ, DPEP3, ICAM2, PACSIN2) were obtained through different analyses, and these genes had predictive validity for PTSD and MDD, playing an important role in the common mechanism of PTSD and MDD. The study findings reveal decreased expression levels of DPEP3, GNAQ, and PACDIN2 in PTSD samples, accompanied by an increased expression of ICAM2. In MDD samples, the expression of DPEP3 and ICAM2 is reduced, whereas GNAQ and PACDIN2 show an increase in expression. This study provides a new perspective on the common molecular mechanisms of PTSD and MDD. These common pathways and core genes may provide promising clues for further experimental studies. • Four hub genes were obtained through different analyses, and these genes had predictive validity for PTSD and MDD. • This study provides a new perspective on the common molecular mechanisms of PTSD and MDD. • These common pathways and hub genes may provide promising clues for further experimental studies. [ABSTRACT FROM AUTHOR]

CD40 is a member of the tumor necrosis factor (TNF) receptor superfamily of receptors expressed on a variety of cell types. The CD40–CD40L interaction gives rise to many immune events, including the licensing of dendritic cells to activate CD8+ effector T cells, as well as the facilitation of B cell activation, proliferation, and differentiation. In malignant cells, the expression of CD40 varies among cancer types, mediating cellular proliferation, apoptosis, survival and the secretion of cytokines and chemokines. Agonistic human anti-CD40 antibodies are emerging as an option for cancer treatment, and early-phase clinical trials explored its monotherapy or combination with radiotherapy, chemotherapy, immune checkpoint blockade, and other immunomodulatory approaches. In this review, we present the current understanding of the mechanism of action for CD40, along with results from the clinical development of agonistic human CD40 antibodies in cancer treatment (selicrelumab, CDX-1140, APX005M, mitazalimab, 2141-V11, SEA-CD40, LVGN7409, and bispecific antibodies). This review also examines the safety profile of CD40 agonists in both preclinical and clinical settings, highlighting optimized dosage levels, potential adverse effects, and strategies to mitigate them. [Display omitted] • CD40L-CD40 signaling plays an intricate role in regulation of immune and malignant cells in the tumor microenvironment. • CD40 is linked to both biological and immunological functions. • Preclinical studies and clinical development of CD40 agonism therapies underscore its significance in cancer treatment. • Careful management of dosage optimization and adverse effects is crucial for future design of CD40 agonism cancer therapy. • Cytokine therapies, RAS/RAF/PI3K pathway targeted therapies, and CART therapies can potentially be incorporated with CD40 agonism therapy. [ABSTRACT FROM AUTHOR]

According to the World Health Organization's world report on hearing, nearly 2.5 billion people worldwide will suffer from hearing loss by 2050, which may contribute to a severe impact on individual life quality and national economies. Sensorineural hearing loss (SNHL) occurs commonly as a result of noise exposure, aging, and ototoxic drugs, and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear, which is mainly triggered by reactive oxygen species accumulation, inflammation, and mitochondrial dysfunction. Though recent advances have been made in understanding the ability of cochlear repair and regeneration, there are still no effective therapeutic drugs for SNHL. Chinese herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western medicine. Herein we present trends in research for Chinese herbal medicine for the treatment of SNHL, and elucidate their molecular mechanisms of action, to pave the way for further research and development of novel effective drugs in this field. Chinese herbal medicine exhibits remarkable therapeutic effects against sensorineural hearing loss with fewer side effects and lower cost, and may be considered a new strategy for new drug development. [Display omitted] [ABSTRACT FROM AUTHOR]

The crucial function of bioactive ligands in the interaction with diverse proteins has garnered significant attention in the fields of pharmacokinetics and pharmacodynamics, hence generating considerable interest in the discipline of medicinal chemistry. To better comprehend its molecular mechanism, we implored a detailed biophysical analyses (using multi-spectroscopic, calorimetric, and computational tools) of the carrier protein Lysozyme, Lyz (also known as "Muramidase") with Yohimbine (Yoh). The binding constant (K) of the Lyz-Yoh complex was estimated to be 105 M−1, exhibiting a progressive decline as temperature increased. The thermodynamic-profiling indicated the binding to be associated with an exothermic interaction driven by entropy. The confirmation of spontaneous binding is evidenced by the observed decrease in free energy. The variation in ionic strength indicated that non-polyelectrolytic forces were involved in the association. In addition, it was investigated how different metal ions affected the Lyz-Yoh binding. Calorimetric studies revealed the binding to be exothermic in nature, which also aligns with spectroscopic data. Results from circular dichroism (CD) experiments, demonstrated the structural alterations brought about in Lyz by Yoh. The likely binding sites and protein residuals to the ligand (Yoh) were illustrated using theoretical techniques, viz., molecular docking and molecular dynamic (MD) simulation. In clinical and pharmaceutical assessments, these metrics are especially relevant for rational drug development. [Display omitted] • Spontaneous and thermodynamically favorable association. • Competition between the metal ions and Yoh binding to Lyz at the same binding site. • A crucial role was played by the hydrophobic forces and hydrogen bonding. • Lyz microenvironmental changes after ligation with Yoh. [ABSTRACT FROM AUTHOR]

Metformin (Met), a first-line management for type 2 diabetes mellitus, has been expansively employed and studied with results indicating its therapeutic potential extending beyond glycemic control. Beyond its established role, this therapeutic drug demonstrates a broad spectrum of action encompassing over 60 disorders, encompassing metabolic conditions, inflammatory disorders, carcinomas, cardiovascular diseases, and cerebrovascular pathologies. There is clear evidence of Met's action targeting specific nodes in the molecular pathways of these diseases and, intriguingly, interactions with the intestinal microbiota and epigenetic processes have been explored. Furthermore, novel Met derivatives with structural modifications tailored to diverse diseases have been synthesized and assessed. This manuscript proffers a comprehensive thematic review of the diseases amenable to Met treatment, elucidates their molecular mechanisms, and employs informatics technology to prospect future therapeutic applications of Met. These data and insights gleaned considerably contribute to enriching our understanding and appreciation of Met's far-reaching clinical potential and therapeutic applicability. [ABSTRACT FROM AUTHOR]

In heart failure with reduced ejection fraction and heart failure with preserved ejection fraction, profound cellular and molecular changes have recently been documented in the failing myocardium. These changes include altered calcium handling and metabolic efficiency of the cardiac myocyte, reactivation of the fetal gene program, changes in the electrophysiological properties of the heart, and accumulation of collagen (fibrosis) at the interstitial level. Cardiac contractility modulation therapy is an innovative device-based therapy currently approved for heart failure with reduced ejection fraction in patients with narrow QRS complex and under investigation for the treatment of heart failure with preserved ejection fraction. This therapy is based on the delivery of high-voltage biphasic electrical signals to the septal wall of the right ventricle during the absolute refractory period of the myocardium. At the cellular level, in patients with heart failure with reduced ejection fraction, cardiac contractility modulation therapy has been shown to restore calcium handling and improve the metabolic status of cardiac myocytes, reverse the heart failure–associated fetal gene program, and reduce the extent of interstitial fibrosis. This review summarizes the preclinical literature on the use of cardiac contractility modulation therapy in heart failure with reduced and preserved ejection fraction, correlating the molecular and electrophysiological effects with the clinical benefits demonstrated by this therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum , was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound. Purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum , was found to promote diabetic wound healing. Schematic illustration of targeted and long-acting regulation mechanism of PC@MLIP MN in T2DM wound healing promotion. PC loaded with macrophage-liposome (MLIP) achieved an accurate regulation on local macrophages, and Gelatin methacryloyl (GelMA)-based microneedles (MNs) promote its skin permeability, which successfully achieved the effect of diabetic wound healing promotion in T2DM mouse models. Figure created with BioRender.com. [Display omitted] [ABSTRACT FROM AUTHOR]

One of the effective methods for the long-term preservation of mammalian genetic resources is the cryopreservation of semen. However, a number of parameters, including diluents, the rate of freezing and thawing, cryoprotectants, etc., can easily alter the survival of frozen-thawed sperm. Numerous studies have documented the addition of a variety of zinc compounds, to the diluents used to cryopreserve sperm. The primary objective of this review is to briefly describe that adding zinc to diluents as an antioxidant significantly enhances frozen-thawed sperm quality. Second, a summary of the present understanding of zinc's molecular mechanism on semen cryopreservation is provided. Thirdly, this study addresses that nanoparticles of zinc can offer suggestions for raising cryopreservation effectiveness. • The supplementation of zinc could act as an antioxidant to improve the quality of frozen-thawed sperm. • The putative mechanisms by which zinc protects boar sperm from cryodamage are shown in the manuscript. • Cryopreservation can be made more effective because of the outstanding qualities of zinc of the nano-type. [ABSTRACT FROM AUTHOR]

WRKY transcription factors (TFs) are transcriptional regulators in plants and have a conserved WRKY motif and various zinc-finger structures. WRKY TFs may integrate signals of pathogen-associated molecular pattern-triggered immunity and effector-triggered immunity. WRKY genes modulate transcription in plant defense responses against environmental stressors like reactive oxygen species burst, Ca2+ influx, mitogen-activated protein kinase activation, phytohormone production, and epigenetic modification. WRKYs may function as master regulators to balance plant growth and stress response. WRKYs could aid the generation of stress-resilient crops by modern molecular breeding for better crop productivity in the face of climate change. Environmental stressors caused by climate change are fundamental barriers to agricultural sustainability. Enhancing the stress resilience of crops is a key strategy in achieving global food security. Plants perceive adverse environmental conditions and initiate signaling pathways to activate precise responses that contribute to their survival. WRKY transcription factors (TFs) are essential players in several signaling cascades and regulatory networks that have crucial implications for defense responses in plants. This review summarizes advances in research concerning how WRKY TFs mediate various signaling cascades and metabolic adjustments as well as how epigenetic modifications involved in environmental stress responses in plants can modulate WRKYs and/or their downstream genes. Emerging research shows that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)-mediated genome editing of WRKYs could be used to improve crop resilience. [ABSTRACT FROM AUTHOR]

Leaf rolling (LR) is one of the defensive mechanisms that plants have developed against adverse environmental conditions. LR is a typical drought response, promoting drought resistance in various gramineae species, including wheat, maize, and rice. Rice cultivation faces the formidable challenge of water deprivation because of its high water requirements, which leads to drought-related symptoms in rice. LR is an important morphological characteristic that plays a key role in controlling water loss during water insufficiency, thereby regulating leaf area and stature, which are crucial agronomic traits determining yield criteria. Bulliform, sclerenchyma, mesophyll, and vascular bundles are the cells that engage in LR and commonly exhibit adaxial or abaxial types of rolling in rice. The specific genes linked to rolling, either adaxially or abaxially, are discussed here. In addition to the factors influencing LR, here is a short review of the morphological, physiological and molecular responses of this adaptation under drought stress. Moreover, this review highlights how LR combats the consequences of drought stress. The eco-physiological and molecular mechanisms underlying this morphological adaptation in rice should be further explored, as they might be useful in dealing with various degrees of drought tolerance. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a pathological condition characterized by replacement of normal liver tissue with scar tissue, and also the leading cause of liver-related death worldwide. During the treatment of liver fibrosis, in addition to antiviral therapy or removal of inducers, there remains a lack of specific and effective treatment strategies. For thousands of years, Chinese herbal medicines (CHMs) have been widely used to treat liver fibrosis in clinical setting. CHMs are effective for liver fibrosis, though its mechanisms of action are unclear. In recent years, many studies have attempted to determine the possible mechanisms of action of CHMs in treating liver fibrosis. There have been substantial improvements in the experimental investigation of CHMs which have greatly promoted the understanding of anti-liver fibrosis mechanisms. In this review, the role of CHMs in the treatment of liver fibrosis is described, based on studies over the past decade, which has addressed the various mechanisms and signaling pathways that mediate therapeutic efficacy. Among them, inhibition of stellate cell activation is identified as the most common mechanism. This article provides insights into the research direction of CHMs, in order to expand its clinical application range and improve its effectiveness. [ABSTRACT FROM AUTHOR]

• Lichens are a symbiotic relationship between two organisms an alga (Phycobiont) and a fungus (Mycobiont). Mycobiont predominates in the lichen thallus and provides its structure, form, as well as texture. Algae contribute to the thallus by providing nutrition. • The potential of lichens for medicinal use is to have a variety of bioactive anticancer compounds. • Synthesized lichen compounds may exhibit a range of bioactive constituents in response to their cytotoxic effects, including antioxidant, antibiotic, antimutagenic, antimicrobial, antibacterial, anti-inflammatory, antipyretic, inhibitory proteins, as well as endogenous plant growth impact. • Lichen derivatives have a wide range of anti-cancer effects against many forms of cancer cell types, like usnic acid, gyrophoric acid, and lechanoric acid. The potential of lichens for medicinal use is to have a variety of bioactive anticancer compounds. Several factors drive the issue of lichens as a usual substance of carcinoma chemicals for lichens. In a variety of climates which could be represented by extreme climatic variables, lichens can endure heat intensities, Ultraviolet rays, limited nutrient uptake, humidity, etc. Their results are obtained is due to the possible defence system they have towards severe change, simultaneously generating bioactive substances with distinctive attributes through different biosynthesis pathways. Synthesized lichen compounds may exhibit a range of bioactive constituents in response to their cytotoxic effects, including antioxidant, antibiotic, antimutagenic, antimicrobial, antibacterial, anti-inflammatory, antipyretic, inhibitory proteins, as well as endogenous plant growth impact. In addition, lichen derivatives have a wide range of anti-cancer effects against many forms of cancer cell types, like usnic acid, gyrophoric acid, and lechanoric acid. Furthermore, when functioning together through human cancer cells, lichens compounds can cause synergistic cytotoxic results. Anti-cancer stimulation of molecular lichen derivatives through the process of cytotoxicity by cellular processes and initiation of cell death and by modulation in immune activity, angiogenesis, or metabolism of energy. This review mainly focuses on the potential role of lichens' active constituents as beneficial moieties to exhibit anticancer activities with their molecular mechanism. [ABSTRACT FROM AUTHOR]

The objective of our study, which combined API-ILs strategy and controlled-release polymers, was to prepare a 72 h long-acting drug-in-adhesive patch for optimum delivery of asenapine (ASE). Special attention was paid to the permeation promotion mechanism and the controlled release behavior of ASE-ILs in pressure sensitive adhesives (PSA). Formulation factors were investigated by ex vivo transdermal experiments. The optimized patch was evaluated by pharmacokinetics study and skin irritation test. The obtained formulation was as follows, 15% w/w ASE-MA (about 1136 μg/cm2 ASE, 413 μg/cm2 MA), AACONH 2 (Amide adhesive) as the matrix, 80 μm thickness, backing film of CoTran™ 9733. The optimized patch displayed satisfactory ex vivo and in vivo performance with Q 72 h of 620 ± 44 µg/cm2 and F abs of 62.4%, which utilization rate (54.6%) was significantly higher than the control group (38.3%). By using the classical shake flask method, 13C NMR, DSC, and FTIR, the physicochemical properties and structure of ILs were characterized. log D o/w , ATR-FTIR, Raman, and molecular dynamics simulation results confirmed that ASE-MA (MA: 3-Methoxypropionic acid) had appropriate lipophilicity, and affected lipid fluidity as well as the conformation of keratin to improve the skin permeation. The FTIR, MDSC, rheology, and molecular docking results revealed that hydrogen bond (H-bond), were formed between ASE-MA and PSA, and the drug increased the molecular mobility of polymer chains. In summary, the 72 h long-acting patch of ASE was successfully prepared and it supplied a reference for the design of long-acting patches with ASE. [Display omitted] [ABSTRACT FROM AUTHOR]

Acupuncture, a traditional oriental intervention for chronic pain, has been gaining worldwide popularity. Transient receptor potential vanilloid subfamily 1 (TRPV1) is a key factor mediating pain production and sensitization. According to multiple studies, TRPV1 is involved the acupuncture-induced relief of pathological pain. Herein, we systematically screened the experimental reports on TRPV1 involvement in acupuncture analgesia, and reviewed the role of TRPV1 in acupuncture in inhibiting different pathological pain and unresolved problems, including inflammatory pain, neuropathic pain, visceral pain, fibromyalgia and cancer pain. At localized acupoints, TRPV1 was involved in the initiation of acupuncture signals. Acupuncture could inhibit the development of pathological pain as well as the transmission of pain signals by suppressing TRPV1 expression and opening activity from the peripheral dorsal root ganglia to the central spinal cord. Furthermore, acupuncture can not only inhibit the expression of TRPV1, but also promote the expression of TRPV1 in the brain to alleviate pain sensation and depression-like behavior. Moreover, the mechanism by which acupuncture regulates TRPV1 may involve neuro-immune crosstalk. In conclusion, the regulation of TRPV1 expression and function may be one of the primary mechanisms by which acupuncture relieves pathological pain, laying the groundwork for future basic research on acupuncture's pain-relieving effects. [ABSTRACT FROM AUTHOR]

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases. An updated ETCM v2.0 database may be a major data warehouse for quality marker identification and pharmacological mechanism investigation of TCMs against human diseases, and TCM-derived drug discovery and repurposing. [Display omitted] [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma(PTC)is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression. [ABSTRACT FROM AUTHOR]

• CUM reduced the initial biofilm production capacity and disrupt the three-dimensional architecture of S. aureus biofilm. • CUM inhibited cell motility, cell surface hydrophobicity and extracellular polymers production of S. aureus. • CUM interfered with the expression of adhesion genes associated with biofilm formation such as agrA, icaA, sigB, ebpS, fnbA, fib and clfA. • CUM bound to SarA by H-bonds to inhibit S. aureus biofilm. In Iranian, ethnopharmacological studies show that Cuminum cyminum is commonly used in pain relief. The most abundant component in C. cyminum seeds is cuminaldehyde (CUM). However, there are few articles that have evaluated the anti-biofilm activity against Staphylococcus aureus (S. aureus). The nobility of this study was to evaluate the anti-biofilm effect of CUM and to investigate its possible mechanism of action. Crystal violet staining assay showed that CUM decreased biofilm biomass. The morphological observation indicated that CUM restrained the adhesion of biofilm, and destroyed the integrated and cohesive structure of biofilm. MTT assay proved that the metabolic activity of adherent cells treated with CUM was reduced. In vitro assays exhibited that cell motility, cell surface hydrophobicity, and extracellular polymers production of S. aureus were also inhibited in the presence of CUM. Furthermore, quantitative real-time PCR analysis confirmed the ability of CUM to interfere with the expression of adhesion genes associated with biofilm formation such as agrA, icaA, sigB, ebpS, fnbA, fib and clfA. Molecular docking speculated that the interaction of CUM with SarA could inhibit SarA-DNA binding, and ultimately inhibit the formation of biofilm. The results of this trial provided scientific experimental data for the use of CUM as an anti-biofilm agent. [ABSTRACT FROM AUTHOR]

• Documentation of neuroprotective potential of licorice as a medicinal plant. • In vivo and in vitro neuroprotection of active constituents isolated from liquorice discussed. • Mode of action of liquorice and its active constituents have been summarized. Conventional natural remedies have been standing out as forthcoming alternatives of treatment for different diseases across several countries. In recent years, restorative plants have been acquiring more acceptance because these plants, as natural items, make less side effects and further develop adequacy in comparison to the chemically synthesized products. Liquorice is such a medicinal plant with unique therapeutic values and applications in conventional pharmacology. Several researches have confirmed its clinical adequacy in various medical conditions, which includes the neuroprotective role of Liquorice and its dynamic components in chronic or acute neurodegenerative cycles, along with its antioxidant, antifungal, anticarcinogenic, anti-inflammatory, and cytotoxic activities. Preclinical discoveries uphold the fact that Liquorice might be a promising remedial choice against neurological problems, with the potential of inhibiting the progression of disease. In the current review, we have discussed the neuroprotective impacts of Liquorice and its components in persistent neurologic problems such as Ischemic stroke, Alzheimer's, Huntington's diseases, and Parkinson's disease both in cellular and molecular level. The study also aims to shed light upon the probable futuristic approaches towards the application and usage of Liquorice. [ABSTRACT FROM AUTHOR]

Recently, research interests are growing regarding the formation and mechanisms of amyloid fibrils from plant proteins. This study investigated the fibrillization kinetics and rheological behaviors of panda bean protein isolate (PBPI) at pH 2.0 and 90 °C for various heating times (0–24 h). Results showed that PBPI formed two distinct classes of fibrils after heating for 10 h, including flexible fibril with a contour length of ∼751 nm, and rigid fibril with periodicity of ∼40 nm. The secondary structural changes during fibril formation were monitored by circular dichroism spectroscopy and indicated that β-sheet content increased first (0−12 h) and then decreased (>12 h), which coincided with similar changes in thioflavin T fluorescence. The gel electrophoresis revealed that the polypeptides of PBPI were progressively hydrolyzed upon heating, and the resulting short fragments were involved in fibril formation rather than PBPI monomer. PBPI-derived fibrils showed extremely high viscosity and storage modulus. A plausible molecular mechanism for PBPI fibrillation process was hypothesized, including protein unfolding, hydrolysis, assembly into matured fibrils, and dissociation of the fibrils. The findings provide useful information to manipulate the formation of legume proteins-based fibrils and will benefit future research to explore their potential applications. [Display omitted] • The self-assembling behavior of PBPI was time-dependent at 90 °C and pH 2.0. • PBPI self-assembled into flexible fibril and rigid fibril. • PBPI-derived fibrils possessed extremely high viscosity. • PBPI-derived fibrils showed excellent gelling performances. • PBPI fibrillation included unfolding and hydrolysis, aggregation, and disintegration. [ABSTRACT FROM AUTHOR]

[Display omitted] The purpose of this study was to prepare a dexmedetomidine (Dex) 72 h long-acting patch by the combined use of ion-pair strategy and chemical enhancers (CEs), and to investigate molecular mechanisms of drug-loading enhancement and controlled release. The formulation of patch was optimized by single-factor investigation and Box-Behnken design. The pharmacokinetics, analgesic pharmacodynamics and irritation of the formulation were evaluated, respectively. Moreover, the effects of ion-pairs and CEs on the patch were characterized by DSC, rheology study, FTIR, and molecular docking, and the effects on the skin were evaluated by Attenuated Total Reflection Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman study, and molecular dynamics, respectively. The optimized formulation was 17.00 % (w/w) Dex-NA (Naphthoic acid), 7.20 % Polyglyceryl-3 dioleate (POCC), 25-AAOH as pressure sensitive adhesives (PSA) and 66.50 μm in thickness. Compared with the control group (C max = 62.02 ± 16.55 ng/mL, MRT 0-t = 26.74 ± 1.27 h), the pharmacokinetics behavior of the optimization group was more stable and durable (C max = 31.22 ± 13.26 ng/mL, MRT 0-t = 33.62 ± 1.62 h). Besides, it also showed good analgesic effect and no obvious irritation. The results indicated that Dex-NA both increased the drug-PSA interactions and inhibited the penetration of the drug into the skin. POCC increased the molecular mobility of the PSA and disrupted skin lipids thereby improving the drug penetration rate. In summary, the Dex long-acting patch was developed, which provided a reference for the combined application of ion-pair strategy and CEs in other long-acting transdermal delivery. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy drugs are widely criticized for their serious side effects and low cure rate. Therefore, adjuvant therapy as a combination with chemotherapy administration is being accepted by many patients. However, unclear drug targets and mechanisms limit the application of adjuvant treatment. In this study, we confirmed TMEM16A is a key drug target for lung adenocarcinoma, and narirutin is an effective anti-lung adenocarcinoma natural product. Virtual screening and fluorescence experiments confirmed that narirutin inhibits the molecular target TMEM16A, which is specific high-expression in lung adenocarcinoma. Molecular dynamics simulations and electrophysiological experiments revealed the precise molecular mechanism of narirutin regulating TMEM16A. The anticancer effect of narirutin and its synergistic effect on cisplatin were explored by cell proliferation, migration, and apoptosis assays. The signaling pathways regulated by narirutin were analyzed by western blot. Tumor xenograft mice experiments demonstrated the synergistic anticancer effect of narirutin and cisplatin, and the side effects of high concentrations of cisplatin were almost eliminated. Pharmacokinetic experiments showed the biological safety of narirutin is satisfactory in vivo. Based on the significant anticancer effect and high biosafety, naringin has great potential as a functional food in the adjuvant treatment of lung cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Copyright of Revue Francaise d'Allergologie is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Natural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs. Our hope is that we can make use of advances in target identification and single-cell multiomics to obtain a deeper understanding of actions of mechanisms of natural products that will allow innovation and revitalization of TCM and its swift industrialization and internationalization. This review proposes new strategies that focus on elucidating the mechanisms of natural products and their target proteins, hoping to provide insights into the development of new drugs based on natural products. [Display omitted] [ABSTRACT FROM AUTHOR]

The molecular mechanism of the formation of protein corona by the interaction of gold nanorods (AuNRs) with fibrinogen and transferrin was studied by spectroscopic methods and molecular docking. Studies have shown that AuNRs can be used as quencher to quench the fluorescence of fibrinogen/transferrin. The quenching mechanism mainly comes from static quenching. Fibrinogen has two different binding sites on the longitudinal and the transverse plane of AuNRs respectively, while transferrin has only one binding site on the surface of AuNRs. The adsorption process conforms to Freundlich adsorption isotherm and the pseudo-second-order reaction. The chemisorption is the rate-limiting step. Fibrinogen/transferrin may be a component of the "hard corona" because they bind AuNRs with high binding affinity. The formation of protein corona leads to a decrease in the hydrophobicity of the microenvironment around transferrin tryptophan (Trp) residues and an increase in the hydrophobicity of the microenvironment around fibrinogen/transferrin tyrosine (Tyr) residues, affecting the tertiary and secondary structure of fibrinogen/transferrin. Molecular docking can clearly see the specific amino acid residues of fibrinogen and transferrin adsorbed on AuNRs, and verify the experimental results. • Fibrinogen has two binding sites, and transferrin has one binding site on AuNRs. • The adsorption process conforms to Freundlich adsorption isotherm model. • The adsorption process conforms to pseudo-second-order reaction model. • Fibrinogen/transferrin may be a component of the hard corona of AuNRs. • The structure of fibrinogen/transferrin is effected by protein corona. [ABSTRACT FROM AUTHOR]

AIDS is a serious disease with impaired immune function caused by human immunodeficiency virus (HIV) infection. The treatment of AIDS has always been the focus of global scientific research, and Tat protein is a key regulatory protein in the process of HIV infection. Its high expression is closely related to virus replication, disease progression, etc. The aim of this study is to explore the molecular mechanism of regulating Tat protein expression by using network pharmacology based traditional Chinese medicine for calming the liver and detoxifying. 129 AIDS patients were enrolled in the study and randomly divided into HAART combined with PGJDP treatment and HAART alone treatment groups. The virological response rate, immunological response status (CD4 + T cell level, CD4/CD8) and incidence of abnormal liver function were observed before and 48 weeks after treatment. Using the TCMSP database to obtain the chemical components and targets of the main traditional Chinese medicine components in PGJDP, clinical results indicate that the combination of HAART and PGJDP treatment can improve the virological response rate (P > 0.05); Increase the number of CD4 + T lymphocytes (P > 0.05); Significantly increased CD4/CD8 ratio (P < 0.01); Simultaneously, it significantly reduced the incidence of liver dysfunction (P < 0.01). After screening and analysis, the Chinese herbal medicine for calming liver and detoxifying has the potential to significantly regulate the expression of Tat protein. These Chinese herbal compounds can reduce the expression of Tat protein by affecting key pathways and regulating the expression of related genes, which has potential therapeutic effects on the treatment of AIDS. [ABSTRACT FROM AUTHOR]

Aging is an unavoidable process marked by numerous physiological and psychological changes that profoundly impact overall health and quality of life. As the global population ages, there is a growing interest in non-pharmacological therapies that can mitigate the adverse effects of aging and promote longevity. This narrative review explores the broad spectrum of non-pharmacological mechanisms offering anti-aging benefits, with a special emphasis on holistic practices such as yoga, meditation, and lifestyle interventions. These therapies influence critical biological processes, including reducing oxidative stress, modulating chronic inflammation, enhancing immune function, and preserving telomere length—key markers of cellular aging. Additionally, these practices contribute to improved cardiovascular health, musculoskeletal strength, and mental well-being, fostering a comprehensive approach to healthy aging. Yoga, for instance, combines physical postures, breath control, and meditation to enhance physical flexibility, mental clarity, and emotional balance. Meditation practices are shown to reduce stress and improve cognitive function, further supporting healthy aging. Lifestyle modifications, such as diet and regular physical activity, complement these therapies by promoting overall vitality and reducing the risk of age-related diseases. This review underscores the potential of integrating these non-pharmacological strategies into daily routines to enhance resilience against aging, improve quality of life, and extend healthspan. Furthermore, it highlights the need for continued research to fully elucidate the mechanisms by which these therapies exert their anti-aging effects and to develop evidence-based guidelines for their implementation. • Yoga plays an important role in preventive health care. • Yoga offers a holistic approach to enhancing physical and mental well-being. • Yoga enhances cognitive function and increases mental acuity. • Yoga is a key component of public health initiatives designed to promote healthy aging. [ABSTRACT FROM AUTHOR]

Algal polysaccharide is an important food functional factor with diverse bioactive and low toxicity. Previous studies have confirmed Caulerpa chemnitzia polysaccharides (CRVP) have immunomodulatory activity, but the immunomodulatory mechanism of CRVP in macrophages has not been thoroughly explored yet. In our research, we found that CRVP has outstanding immunomodulatory activity in macrophages, which is reflected in promoting cell proliferation, upregulating cytokines (IL-1β, IL-6, and TNF-α) expression, and increasing NO and ROS levels. Additionally, the result of joint analysis of untargeted metabolomics showed metabolism played a major role in the immunomodulatory of CRVP and suggested succinic acid was a key metabolite. Further verification indicated that the accumulation of succinic acid in macrophages after administered with CRVP, induced the down-regulation of prolyl hydroxylase domain 2 (PHD2) and up-regulation of hypoxia-inducible factor-1α (HIF-1α), thereby enhancing IL-1β expression. Together, the immunomodulatory activity of CRVP in macrophages via succinate/PHD2/HIF-1α/IL-1β pathway. • CRVP has significant immunomodulatory activity. • CRVP promotes macrophage proliferation and expression of pro-inflammatory mediators such as IL-1β, IL-6, TNF-α, NO and ROS. • Metabolite succinic acid involved in the immunomodulatory effect of CRVP in macrophages. • CRVP exerts immunomodulatory effects in macrophages via succinate/PHD2/HIF-1α/IL-1β pathway. [ABSTRACT FROM AUTHOR]

Cationic and anionic castor oil-based waterborne polyurethanes (C-WPU/A and C-WPU/C) have great potential for development in agriculture. However, it is still unclear whether these polyurethanes are harmful or toxic to soil fauna. Based on multilevel toxicity endpoints and transcriptomics, we investigated the effects of C-WPU/A and C-WPU/C on earthworms (Eisenia fetida). The acute toxicity results showed that C-WPU/A was highly toxic to the earthworms, whereas C-WPU/C was nearly nontoxic. C-WPU/A significantly affected the body weight, burrowing ability and cocoon production rate of earthworms compared to C-WPU/C. After exposure to C-WPU/A, the results showed accumulation of reactive oxygen species (ROS), abnormal peroxidase activity, and increased malondialdehyde levels. Additionally, more serious histopathological damage was observed in earthworms, such as epidermal damage, vacuolization, longitudinal muscle disorganization, and shedding of intestinal epidermal cells. At the cellular level, C-WPU/A induced more severe lysosomal damage, DNA damage and apoptosis than C-WPU/A. C-WPU/A made more differentially expressed genes and considerably more enriched pathways at the transcriptional level than C-WPU/C. These pathways are largely involved in cell membrane signaling, detoxification, and apoptosis. These results provide an important reference for elucidating the selective toxicity mechanisms of C-WPU/A and C-WPU/C in earthworms. [Display omitted] • Selective toxicity of C-WPU/A and C-WPU/C on earthworms (toxicity: C-WPU/A > C-WPU/C). • C-WPU/C is precipitated and shed by the mucus of earthworms, thus avoiding toxic effects. • C-WPU/A breaks through the mucus and penetrates the epidermal cells into the earthworm's body. • C-WPU/A induced more severe tissue damage, apoptosis, DNA damage and disordered gene expression. [ABSTRACT FROM AUTHOR]

Here, we subjected the marine copepod Tigriopus japonicus to environmentally-relevant concentrations of microplastics (MPs) and mercury (Hg) for three generations (F0–F2) to investigate their physiological and molecular responses. Hg accumulation and phenotypic traits were measured in each generation, with multi-omics analysis conducted in F2. The results showed that MPs insignificantly impacted the copepod's development and reproduction, however, which were significantly compromised by Hg exposure. Interestingly, MPs significantly increased Hg accumulation and consequently aggravated this metal toxicity in T. japonicus , demonstrating their carrier role. Multi-omics analysis indicated that Hg pollution produced numerous toxic events, e.g., induction of apoptosis, damage to cell/organ morphogenesis, and disordered energy metabolism, ultimately resulting in retarded development and decreased fecundity. Importantly, MPs enhanced Hg toxicity mainly via increased oxidative apoptosis, compromised cell/organ morphogenesis, and energy depletion. Additionally, phosphoproteomic analysis revealed extensive regulation of the above processes, and also impaired neuron activity under combined MPs and Hg exposure. These alterations adversely affected development and reproduction of T. japonicus. Overall, our findings should offer novel molecular insights into the response of T. japonicus to long-term exposure to MPs and Hg, with a particular emphasis on the carrier role of MPs on Hg toxicity. [Display omitted] • Copepod's multigenerational exposure to MPs and Hg was performed. • MPs insignificantly impacted the copepod's development and reproduction. • MPs increased Hg toxicity to the growth/reproduction in copepods. • Hg-induced compromised traits were linked to energy depletion and high apoptosis. • MPs enhanced Hg toxicity by high oxidative apoptosis and impaired neuron activity. [ABSTRACT FROM AUTHOR]

Feed efficiency (FE) is an important economic factor in poultry production, and feed conversion ratio (FCR) is one of the most widely used measures of FE. Factors associated with FCR include genetics, the environment, and other factors. However, the mechanisms responsible for FCR in chickens are still less well appreciated. In this study, we examined the pattern changes of FCR, then delved into understanding the mechanisms behind these variations from both genetic and environmental perspectives. Most interestingly, the FCR at the front section of henhouse exhibited the lowest value. Further investigation revealed that laying rate in the high FCR (HFCR) group was lower than that in the low FCR (LFCR) group (P < 0.05). Cortisol, total antioxidant capacity (TAOC), and IgG levels in the LFCR group were significantly lower than those in the HFCR group (P < 0.05), while BUN level was significantly higher than that in the HFCR group (P < 0.05). We identified a total of 67 and 10 differentially expressed genes (DEGs) associated with FCR in ovarian and small intestine tissues, respectively. Functional enrichment analysis of DEGs revealed that they might affect FCR by modulating genes associated with salivary secretion, ferroptosis, and mineral absorption. Moreover, values for relative humidity (RH), air velocity (AV), PM 2.5 , ammonia (NH 3), and carbon dioxide (CO 2) in the LFCR group were significantly lower than those in the HFCR group (P < 0.05). Conversely, value for light intensity (LI) in the LFCR group was significantly higher than that in the HFCR group (P < 0.05). Correlation analysis revealed a positive correlation between FCR and RH, AV, PM 2.5 , NH 3 , and CO 2 , and a negative correlation with LI. Finally, the FCR prediction model was successfully constructed based on multiple environmental variables using the random forest algorithm, providing a valuable tool for predicting FCR in chickens. [ABSTRACT FROM AUTHOR]

The dried rhizomes of Paris yunnanensis Franch. have been extensively utilized in traditional Chinese medicine as hemostatic, antitumor, and antimicrobial agents. An examination of classical texts and renowned Chinese medical formulations showcased its efficacy in acne treatment. Presently, there is a significant scarcity of Paris resources. Consider directing attention towards the non-medicinal parts of Paris to mitigate the strain on medicinal resources within this realm. To address these resource limitations, this study investigated the bioactivity and pharmacodynamics of the above-ground parts of Paris (AGPP). A synergistic approach integrating network pharmacology, molecular docking (in silico validation), and animal experimentation (in vivo validation) was employed to elucidate the potential mechanisms underlying the efficacy of AGPP against acne vulgaris in this study. The active constituents in AGPP extracts were identified via UHPLC-Q-Orbitrap HRMS analysis, with their targets extracted for network pharmacological analysis. KEGG pathway analysis unveiled potential therapeutic mechanisms, validated through molecular docking and rat auricular acne model experiments. Comprehensive chemical characterization revealed fifty constituents, including steroidal saponins, flavonoids, amino acids, organic acids, phytohormones, phenolic acids, and alkaloids. Diosgenin, Quercetin, Kaempferol, Ecdysone, and α-linolenic acid were identified as main constituents with acne-treating potential. Core targets included SRC, MAPK3, and MAPK1, with key signaling pathways implicated. Histologically, AGPP mitigated acne-induced follicular dilatation and inflammation, inhibiting inflammatory cytokine production (IL-6, IL-1β, TNF-α). This study offers insight into AGPP's mechanism for acne treatment, laying groundwork for Paris development and drug discovery. [Display omitted] [ABSTRACT FROM AUTHOR]

Lycium barbarum L. is of great significance medicinal and edible plant, which is native to N. & Central China. The extensive health benefits of L. barbarum have earned it great respect in traditional medicine for centuries. Lycium barbarum polysaccharides (LBPs) being recognized as one of the most crucial bioactive compounds found within this plant, with it exhibit a diverse range of pharmacological activities and nutritional functions, thereby generating substantial market demand and broad application prospects. To gain a more comprehensive understanding of LBPs, the review discussed the extraction, purification and structural-property relationships of these compounds. In addition, this review provides a comprehensive summary of the potential mechanisms underlying various biological activities attributed to LBPs, including immune modulation, antioxidant effects, neuroprotection, hepatoprotection, and antitumor properties. The application status and the future research directions of LBPs were subsequently presented. This review will establish a robust foundation and serve as an invaluable resource for future research and advancements in the field of LBPs. [Display omitted] • The current research focuses on the extraction methods, structural complexities, and pharmacological mechanisms of LBPs. • LBPs are key bioactive ingredients exhibiting pharmacological actions such as immunomodulation, antioxidation, neuroprotection, hepatoprotection, and antitumor activities. • This review highlights the potential and role of LBPs in medicine, health food, and materials, envisioning a future where it becomes an essential component of modern healthcare. [ABSTRACT FROM AUTHOR]

The dose effect of radiation has long been a topic of concern, but the molecular mechanism behind it is still unclear. In this study, dried pea seeds were irradiated with 252Cf fission neutron source. Through analyzing the transcriptome and proteome of M 1 generation pea (Pisum sativum L.) leaves, we studied the molecular rule and mechanism of neutron dose effect. Our results showed three important rules of global gene expression in the studied dose range. The rule closely related to the neutron absorbed dose at the transcription and translation levels is: the greater the difference in neutron absorbed dose between two radiation treatment groups, the greater the difference in differential expression between the two groups and the control group. We also obtained important sensitive metabolic pathways of neutron radiation, as well as related key genes. Furthermore, the overall molecular regulation mechanism of dose effect was revealed based on the main functional items obtained. Our research results can be applied to appropriate radiation dose estimation and agricultural production practice. • Three important rules of global gene expression in the studied dose range were found. • The overall molecular regulation mechanism of neutron dose effect was revealed. • Phenylpropanoid biosynthesis is sensitive metabolic pathway for neutron radiation. • Carotenoid biosynthesis is downregulated metabolic pathway by neutron radiation. • Some related sensitive key genes of 4Gy and 6Gy neutron irradiation were identified. [ABSTRACT FROM AUTHOR]

Biotechnology provides alternatives for regenerative medicine with more controllable functions. Herein, the polypeptides encoded with human collagen I amino-acid sequences were studied for the first time to modulate biomimetic hydroxyapatite (HAP). With a length of 50–100 nm and a width of 20–30 nm, the HAP crystal formed was plate-like. The interaction of the human collagen sequence polypeptide on the (001), (100), and (211) crystal faces of HAP crystal had been studied using Molecular Dynamics (MD) simulations, respectively. Based on MD simulations, van der Waals forces and hydrogen bonds are the main interactions between polypeptides and HAP through the –NH 2 , –CH 2 –, –OH, and –COOH, respectively. According to the calculated results, der Waals forces might be the main interaction. The human collagen sequence polypeptides exhibited the highest adsorption energy on the (001) plane of HAP, significantly higher than any of the adsorption energy on the (100) and (211) planes. Therefore, the growth of the (001) would be inhibited, which kept accurate with the result of images from the Transmission Electron Microscope (TEM). Study results provide a basis for rational designing of peptides with human collagen sequences to regenerate hard tissues. [ABSTRACT FROM AUTHOR]

Microglia are primarily involved in inflammatory reactions and oxidative stress in the brain; as such reducing microglial activation has been proposed as a potential therapeutic strategy for neurodegenerative disorders. Herein, we investigated the anti-inflammatory and antioxidant activities of coniferaldehyde (CFA), a naturally occurring cinnamaldehyde derivative, on activated microglia to evaluate its therapeutic potential. CFA inhibited the production of nitric oxide (NO) and proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6, in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. CFA also inhibited intracellular reactive oxygen species levels and oxidative stress markers such as 4-HNE and 8-OHdG. Detailed mechanistic studies showed that CFA exerted anti-inflammatory effects by inhibiting TAK1-mediated MAP kinase/NF-κB activation and upregulating AMPK signaling pathways. In addition, CFA exerted antioxidant effects by inhibiting the NADPH oxidase subunits and by increasing the expression of antioxidant enzymes such as HO-1, NQO1, and catalase by upregulating Nrf2 signaling. Finally, we confirmed the effects of CFA on the brains of the LPS-injected mice. CFA inhibited microglial activation and the expression of proinflammatory markers and increased Nrf2-driven antioxidant enzymes. Furthermore, CFA inhibited the production of 4-HNE and 8-OHdG in the brains of LPS-injected mice. As a result, CFA's significant anti-inflammatory and antioxidant properties may have therapeutic applications in neuroinflammatory disorders related with oxidative stress and microglial activation. [Display omitted] • CFA exerted anti-inflammatory and antioxidant effects on LPS-stimulated microglia. • CFA inhibited microglial activation in the brain of LPS-injected mice. • Multiple signaling pathways are involved in the effects of CFA. • AMPK/Nrf2 signaling is key to CFA's anti-inflammatory and antioxidant effects. • Thus, CFA may have therapeutic potential for treating neuroinflammatory disorders. [ABSTRACT FROM AUTHOR]

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is a widely studied plant that shows potential in treating urinary diseases. Previous studies have focused on its chemical composition, pharmacological effects, and clinical applications. This review aims to provide a comprehensive summary and evaluation of the existing literature on CS. It also suggests future research directions to increase our understanding of its medicinal value. 129 pieces of literature were selected from several databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Database, and Google Scholar, and were analyzed. Forty-five active compounds of CS have pharmacological effects such as lowering uric acid, anti-inflammation, anti-oxidation, and kidney protection. The potential mechanisms of these effects may be related to inhibiting transforming growth factor β1 (TGF-β1) activation, reducing inflammatory factors such as IL-8, IL-1β, TNF-α, PGE2, IFN-γ, and IL-6 levels, suppressing the activation of NF-κB, JAK/STAT pathway, enhancing the clearance of ROS, MDA DPPH·, and O 2 ̇ −, and regulating the expression of apoptosis-related pathways and proteins. This paper also discusses the quality control of CS and its efficacy and safety in treating urinary diseases. The study concludes that CS has a high potential for treating urinary diseases. Future studies should focus on observing the metabolic changes of CS active compounds in vivo and investigating the effects of CS on key signaling pathways. Additionally, more standardized and reasonable clinical studies and safety evaluation experiments should be conducted to obtain more clinical data. [Display omitted] • The mechanism of CS treatment in urinary disease was summarized. • Summarized the role of active constituents or sites of CS in underlying mechanisms. • It presents conclusions about the cytokine changes observed in patients after applying CS. • The assistant therapy action and side effect evaluation of CS were discussed in detail. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid-β outside neurons and Tau protein inside neurons. Various pathological mechanisms are implicated in AD, including brain insulin resistance, neuroinflammation, and endocrinal dysregulation of adrenal corticosteroids. These factors collectively contribute to neuronal damage and destruction. Recently, bile acids (BAs), which are metabolites of cholesterol, have shown neuroprotective potential against AD by targeting the above pathological changes. BAs can enter the systematic circulation and cross the blood–brain barrier, subsequently exerting neuroprotective effects by targeting several endogenous receptors. Additionally, BAs interact with the microbiota–gut–brain (MGB) axis to improve immune and neuroendocrine function during AD episodes. Gut microbes impact BA signaling in the brain through their involvement in BA biotransformation. In this review, we summarize the role and molecular mechanisms of BAs in AD while considering the MGB axis and propose novel strategies for preventing the onset and progression of AD. [Display omitted] • Alzheimer's disease is found to be associated with bile acids. • Bile acids can indirectly exert neuroprotective effects in Alzheimer's disease through bidirectional interaction with the microbiota-gut-brain axis. • Gut dysbiosis can lead to neurodegeneration. • Bile acid preparations, probiotics, prebiotics, postbiotics, anti-inflammatory therapy provide direction for the novel therapeutic strategies of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX), a commonly used chemotherapy drug, is hindered due to its tendency to induce cardiotoxicity (DIC). Ferroptosis, a novel mode of programmed cell death, has received substantial attention for its involvement in DIC. Recently, natural product-derived ferroptosis regulator emerged as a potential strategy for treating DIC. In this review, a comprehensive search was conducted across PubMed, Web of Science, Google Scholar, and ScienceDirect databases to gather relevant articles on the use of natural products for treating DIC in relation to ferroptosis. The available papers were carefully reviewed to summarize the therapeutic effects and underlying mechanisms of natural products in modulating ferroptosis for DIC treatment. It was found that ferroptosis plays an important role in DIC pathogenesis, with dysregulated expression of ferroptosis-related proteins strongly implicated in the condition. Natural products, such as flavonoids, polyphenols, terpenoids, and quinones can act as GPX4 activators, Nrf2 agonists, and lipid peroxidation inhibitors, thereby enhancing cell viability, attenuating myocardial fibrosis, improving cardiac function, and suppressing ferroptosis in both in vitro and in vivo models of DIC. This review demonstrates a strong correlation between DOX-induced cardiac ferroptosis and key proteins, such as GPX4, Keap1, Nrf2, AMPK, and HMOX1. Natural products are likely to exert therapeutic effects against DIC by modulating the activity of these proteins. [Display omitted] • Ferroptosis plays a vital role in the pathogenesis of doxorubicin-induced cardiotoxicity. • Targeting ferroptosis as a promising therapeutic strategy for doxorubicin-induced cardiotoxicity. • Natural products hold potential as ferroptosis regulators in doxorubicin-induced cardiotoxicity. • Diverse therapeutic effects and multifaceted mechanisms of natural products in ferroptosis modulation. [ABSTRACT FROM AUTHOR]

Over the years, a plethora of materials – natural and synthetic – have been engineered for the sorption of substance molecules. Porous starch-based sorbents could improve storage stability and release kinetics of substances. Despite the development of rationally designed porous starch sorbents, only a handful of such formulations have been successfully translated into industrial sorption due to unsatisfactory sorption rates. The surface chemistry of these sorbents and the sorption process affect their sorption properties, which may significantly modulate the sorption rates and alter the expected results. This review emphasizes the influence of sorption behavior and sorption forces of porous starch sorbents on their interaction with sorbed substances. We will discuss in depth how the variables involved (surface chemical modification, composite synthesis, sorption process improvement) would improve the sorption rates of porous starch sorbent on sorbates and the mechanisms underlying these effects. In summary, we overview the design considerations based on sorption enhancement and provide a conceptual template for achieving payload. The knowledge gained is essential to ensure optimal sorption characteristics and thereby controlled functioning as intended. [Display omitted] • Non-covalent forces between porous starch materials and sorbate are summarized. • Sorption improvement strategy and molecular mechanism were reviewed. • Industrial application and prospect of porous starch were reviewed. [ABSTRACT FROM AUTHOR]

Tagetes patula L. (T. patula) is a Cd hyperaccumulator plant with high ornamental value and strong resistance. Understanding the molecular mechanisms of Cd tolerance in hyper-accumulating plants is important for improving phytoremediation efficiency. This investigation studied to how Cd affected T. patula 's physiological characteristics and molecular alterations. With the increase of Cd concentration, chlorophyll content, and root biomass decreased; the activities of antioxidant enzymes such as GST, SOD and POD increased. Initially, Cd accumulated mainly in the root and then transferred upward to the leaves. The molecular mechanisms of T. patula after 150 mg/kg and 250 mg/kg treatments were analyzed by transcriptome. In total, 5429 and 6546 differentially expressed unigenes were identified. Phenylpropanoid biosynthesis and phenylalanine metabolism were identified as key pathways in reaction to Cd stress. In addition, many differential genes involved in the response to Cd stress were identified, including heavy metal transporter protein genes, genes and transcription factors related to Cd detoxification. These results indicate that the response of T. patula to Cd was multifaceted, laying the foundation for studies to improve its tolerance to toxic metals. [Display omitted] • Antioxidant enzymes and GSH were increased under Cd stress. • T. patula has a strong capacity for Cd accumulation and translocation. • Many genes were identified as Cd-induced differentially expressed genes. • Phenylpropanoid metabolism play important roles in Cd tolerance in T. patula. [ABSTRACT FROM AUTHOR]

[Display omitted] Chimeric antigen receptor (CAR)-engineered T cells have been defined as 'living drug'. Adding a co-stimulatory domain (CSD) has enhanced the anti-hematological effects of CAR-T cells, thereby elevating their viability for medicinal applications. Various CSDs have helped prepare CAR-T cells to study anti-tumor efficacy. Previous studies have described and summarized the anti-tumor efficacy of CAR-T cells obtained from different CSDs. However, the underlying molecular mechanisms by which different CSDs affect CAR-T function have been rarely reported. The role of CSDs in T cells has been significantly studied, but whether they can play a unique role as a part of the CAR structure remains undetermined. Here, we summarized the effects of CSDs on CAR-T signaling pathways based on the limited references and speculated the possible mechanism depending on the specific characteristics of CAR-T cells. This review will help understand the molecular mechanism of CSDs in CAR-T cells that exert different anti-tumor effects while providing potential guidance for further interventions to enhance anti-tumor efficacy in immunotherapy. [ABSTRACT FROM AUTHOR]

[Display omitted] • AH treatment down-regulated the genes related to respiratory metabolism. • AH treatment down-regulated the genes involved in lignin biosynthesis. • AH treatment down-regulated the genes associated with anthocyanin biosynthesis. • AH treatment down-regulated the genes associated with ROS generation and disease resistance. • AH treatment up-regulated the genes related to ROS elimination. The molecular mechanism underlying the preserving superior quality attributes of postharvest Huping jujube fruit by combining acidic electrolyzed water and high-voltage electrostatic field (AH) treatment remained unclear. The high-throughput sequencing analysis revealed a total of 3590 common differentially expressed genes (DEGs) in the T-W-CK0 vs T-W-CK75 and T-W-CK75 vs T-W-AH75 groups. AH treatment down-regulated most genes associated with respiratory metabolism, as well as lignin and anthocyanin biosynthesis, thereby maintaining lower physiological activities, improving taste and color quality of mature-white jujube. Additionally, AH treatment downregulated the genes involved in reactive oxygen species (ROS) generation and disease resistance, while simultaneously upregulating the genes associated with ROS elimination. This suggested that AH treatment could inhibit pathogen infection to prevent the activation of plants' active defense and reduce the ROS-induced damage. In sum, the present study provided a comprehension explanation that AH treatment improved the storage quality attributes of jujube fruit at the genetic level. [ABSTRACT FROM AUTHOR]

Food safety is closely linked to human health. Thiabendazole is widely used as a fungicide and deodorant on agricultural products like vegetables and fruits to prevent fungal infections during transport and storage. This study aims to investigate the toxicity and potential mechanisms of Thiabendazole using novel network toxicology and molecular docking techniques. First, the ADMETlab2.0 and ADMETsar databases, along with literature, predicted Thiabendazole's potential to induce cancer and liver damage. Disease target libraries were constructed using GeneCards and TCMIP databases, while Thiabendazole target libraries were constructed using Swiss Target Prediction and TCMIP databases. The Venn database identified potential targets associated with Thiabendazole-induced cancer and liver injury. Protein-protein interaction (PPI) networks were derived from the STRING database, and gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways were obtained from the DAVID database. Molecular docking assessed the binding affinity between Thiabendazole and core targets. The study revealed 29 potential targets for Thiabendazole-induced cancer and 30 potential targets for liver injury. PPI identified 5 core targets for Thiabendazole-induced cancers and 4 core targets for induced liver injury. KEGG analysis indicated that Thiabendazole might induce gastric and prostate cancer via cyclin-dependent kinase 2 (CDK2) and epidermal growth factor receptor (EGFR) targets, and liver injury through the same targets, with the p53 signaling pathway being central. GO analysis indicated that Thiabendazole-induced cancers and liver injuries were related to mitotic cell cycle G2/M transition and DNA replication. Molecular docking showed stable binding of Thiabendazole with core targets including CDK1, CDK2, EGFR, and checkpoint kinase 1 (CHEK1). These findings suggest Thiabendazole may affect the G2/M transition of the mitotic cell cycle through the p53 signaling pathway, potentially inducing cancer and liver injury. This study provides a theoretical basis for understanding the potential molecular mechanisms underlying Thiabendazole toxicity, aiding in the prevention and treatment of related diseases. Additionally, the network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized agricultural chemicals. [Display omitted] • First use network toxicology and molecular docking to analyze Thiabendazole's toxicity. • CDK2, EGFR, CCNB1, and CHEK1 work together to cancer and liver injury. • Explored the toxicity of a compound from multiple targets and multiple diseases. • Promote this new technique to assess the mechanisms of toxicity of agrochemicals. [ABSTRACT FROM AUTHOR]