KAT2A-mediated succinylation modification of notch1 promotes the proliferation and differentiation of dental pulp stem cells by activating notch pathway.

BACKGROUND: Dental pulp stem cells (DPSCs) are a kind of undifferentiated dental mesenchymal stem cells with strong self-renewal ability and multi-differentiation potential. This study aimed to investigate the regulatory functions of succinylation modification in DPSCs. METHODS: DPSCs were isolated from the dental pulp collected from healthy subjects, and then stem cell surface markers were identified using flow cytometry. The osteogenic differentiation ability of DPSCs was verified by alkaline phosphatase (ALP) and alizarin red staining methods, while adipogenic differentiation was detected by oil red O staining. Meanwhile, the mRNA of two desuccinylases (SIRT5 and SIRT7) and three succinylases (KAT2A, KAT3B, and CPT1A) in DPSCs before and after mineralization induction were detected using quantitative real-time PCR. The cell cycle was measured by flow cytometry, and the expression of bone-specific genes, including COL1a1 and Runx2 were evaluated by western blotting and were combined for the proliferation and differentiation of DPSCs. Co-immunoprecipitation (co-IP) and immunofluorescence were combined to verify the binding relationship between proteins. RESULTS: The specific markers of mesenchymal stem cells were highly expressed in DPSCs, while the osteogenic differentiation ability of isolated DPSCs was confirmed via ALP and alizarin red staining. Similarly, the oil red O staining also verified the adipogenic differentiation ability of DPSCs. The levels of KAT2A were found to be significantly upregulated in mineralization induction, which significantly decreased the ratio of G0/G1 phase and increased S phase cells; converse results regarding cell cycle distribution were obtained when KAT2A was inhibited. Moreover, overexpression of KAT2A promoted the differentiation of DPSCs, while its inhibition exerted the opposite effect. The elevated KAT2A was found to activate the Notch1 signaling pathway, which succinylated Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. The co-IP results showed that KAT2A and Notch1 were endogenously bound to each other, while inhibition of Notch1 reversed the effects of KAT2A overexpression on the DPSCs proliferation and differentiation. CONCLUSION: KAT2A interacted directly with Notch1, succinylating the Notch1 at the K2177 site to increase their corresponding protein levels in DPSCs. Similarly, KAT2A-mediated succinylation modification of Notch1 promotes the DPSCs proliferation and differentiation, suggesting that targeting KAT2A and Notch1 may contribute to tooth regeneration.

A novel dual-channel cassava starch/polyvinyl alcohol-based film for visual monitoring of shrimp freshness.

In this study, the polyvinylpyrrolidone-alizarin nanoparticles (PVP-AZ NPs) with favorable water dispersion and the carbon quantum dots (RQDs) with aggregate induced emission effect were synthesized to construct an eco-friendly film for food freshness monitoring. The introduction of PVP-AZ NPs and RQDs enhanced the network structure and thermal stability of the cassava starch/polyvinyl alcohol film, and reduced its crystallinity and light transmittance via non-covalent binding with the film-forming matrix. The developed film exhibited visually recognizable colorimetric and fluorescent responses to ammonia at 0.025-25 mg/mL, and it can be reused at least 6 times. Practical application experiment proved that the film, as an indicator label, can achieve accurate, real-time, and visual dynamic monitoring of the freshness of shrimp stored at 25 °C, 4 °C, and - 20 °C under daylight (orange yellow to purple) and UV light (red to blue). The integration of multivariate detection technology can eliminate the interference of external factors by self-correction to improve sensitivity and reliability, which provides a reference for the development of other food quality and safety monitoring platforms.

Mid-infrared spectroscopic identification of the right-baked rhubarb for ulcerative colitis therapy.

Clinical and experimental evidences have confirmed the significant therapeutic effects of rhubarb on ulcerative colitis (UC), but the strong purgative function of rhubarb also aggravates UC symptoms such as bloody diarrhea. Stir-baking to scorch is a traditional Chinese medicinal processing method that can eliminate the adverse purgative function while keep or even enhance the UC therapeutic function of rhubarb. However, the under-baked rhubarb still have the undesirable purgative function, but the over-baked rhubarb may lose the required medicinal functions. Therefore, the determination of the right endpoint is the primary quality concern about the baking process of rhubarb. In this research, typical anthraquinone compounds and mid-infrared (MIR) spectra were recruited to determine the best baking degree of rhubarb for UC therapy. Raw rhubarb slices were baked at 180 °C with rotation to prepare the rhubarbs with different baking degrees. The right-baked rhubarb was defined according to the UC therapeutic responses as well as the traditional color criterion. Referring to the typical anthraquinone compounds in rhubarb slices and extracts, the baking degree of rhubarb may be assessed by the conversion ratio of anthraquinone glycosides to anthraquinone aglycones. MIR spectra showed the gradual decompositions of organic compounds including anthraquinone glycosides and tannins during the baking process. Rhubarbs with different baking degrees can be distinguished clearly by MIR-based principal component analysis. In conclusion, the ratio of anthraquinone glycosides to anthraquinone aglycones may be a reasonable chemical indicator of the right-baked rhubarb. Meanwhile, MIR spectroscopy can identify the right-baked rhubarb simply and rapidly.

Advances in Small Molecular Agents against Oral Cancer.

Oral cancer is a common malignancy with a high mortality rate. Although surgery is the best treatment option for patients with cancer, this approach is ineffective for advanced metastases. Molecular agents are irreplaceable in preventing and treating distant metastases. This review aims to summarise the molecular agents used for the treatment of oral cancer in the last decade and describe their sources and curative effects. These agents are classified into phenols, isothiocyanates, anthraquinones, statins, flavonoids, terpenoids, and steroids. The mechanisms of action of these agents include regulating the expression of cell signalling pathways and related proteases to affect the proliferation, autophagy, migration, apoptosis, and other biological aspects of oral cancer cells. This paper may serve as a reference for subsequent studies on the treatment of oral cancer.

A chromosome-level genome reveals genome evolution and molecular basis of anthraquinone biosynthesis in Rheum palmatum.

BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.

A novel and efficient voltammetric sensor for the simultaneous determination of alizarin red S and tartrazine by using poly(leucine) functionalized carbon paste electrode.

In the current work, a rapid, selective, and sensitive technique was developed for the detection of Alizarin Red S (ARS) by applying poly leucine modified carbon paste electrode (PLMCPE). Electrochemical impedance spectroscopy (EIS) and Scanning electron microscopy (SEM) were utilized to study the surface morphology of unmodified carbon paste electrode (UMCPE) and PLMCPE. The active surface area for UMCPE and PLMCPE was found to be 0.0012 cm2 and 0.0026 cm2 respectively. The electrochemical response of ARS at UMCPE and PLMCPE was analyzed using cyclic voltammetry (CV) in the potential window of 0.4 to 1.0 V. The cyclic voltammogram obtained for varying the pH of 0.2 M phosphate buffer (PB) solution showed maximum current for the oxidation of ARS at pH 6.5. The electrochemical reaction of ARS was found to be irreversible and adsorption controlled. The effect of variation of concentration of ARS on the oxidation peak current was evaluated using CV and linear scan voltammetry (LSV). A linear relationship between the concentration variation and current was obtained in the linear range of 1.5 µM-3.5 µM and 0.2 µM-5.0 µM for CV and LSV respectively. The limit of detection (LOD) of 0.68 µM for the CV method and 0.29 µM for the LSV method was exhibited by the developed sensor. The simultaneous study of ARS along with tartrazine (TZ) showed good selectivity for ARS. The interferents of foreign molecules showed no effect on the selectivity of the electrode. The applicability of PLMCPE on real samples gave good recovery ranging from 97.46-101.2%; hence, the sensor can be utilized on real samples. The developed sensor has good stability and sensitivity.

Exploring the potential of Aspergillus wentii: secondary metabolites and biological properties.

Fungi are of considerable importance due to their capacity to biosynthesize various secondary metabolites with bioactive properties that draw high attention in new drug discovery with beneficial uses for improving human well-being and life quality. Aspergillus genus members are widespread and cosmopolitan species with varying economic significance in the fields of industry, medicine, and agriculture. Its species are renowned for their biosynthesis of secondary metabolites, characterized by both potent biological activity and structural novelty, making them a substantial reservoir for the development of new pharmaceuticals. The current work aimed at focusing on one species of this genus, Aspergillus wentii Wehmer, including its reported secondary metabolites in the period from 1951 to November 2023. A total of 97 compounds, including nitro-compounds, terpenoids, anthraquinones, xanthones, benzamides, and glucans. A summary of their bioactivities, as well as their biosynthesis was highlighted. Additionally, the reported applications of this fungus and its enzymes have been discussed. This review offers a useful reference that can direct future research into this fungus and its active metabolites, as well as their possible pharmacological and biotechnological applications.

An overview of the two-component system GarR/GarS role on antibiotic production in Streptomyces coelicolor.

The Streptomyces genus comprises Gram-positive bacteria known to produce over two-thirds of the antibiotics used in medical practice. The biosynthesis of these secondary metabolites is highly regulated and influenced by a range of nutrients present in the growth medium. In Streptomyces coelicolor, glucose inhibits the production of actinorhodin (ACT) and undecylprodigiosin (RED) by a process known as carbon catabolite repression (CCR). However, the mechanism mediated by this carbon source still needs to be understood. It has been observed that glucose alters the transcriptomic profile of this actinobacteria, modifying different transcriptional regulators, including some of the one- and two-component systems (TCSs). Under glucose repression, the expression of one of these TCSs SCO6162/SCO6163 was negatively affected. We aimed to study the role of this TCS on secondary metabolite formation to define its influence in this general regulatory process and likely establish its relationship with other transcriptional regulators affecting antibiotic biosynthesis in the Streptomyces genus. In this work, in silico predictions suggested that this TCS can regulate the production of the secondary metabolites ACT and RED by transcriptional regulation and protein-protein interactions of the transcriptional factors (TFs) with other TCSs. These predictions were supported by experimental procedures such as deletion and complementation of the TFs and qPCR experiments. Our results suggest that in the presence of glucose, the TCS SCO6162/SCO6163, named GarR/GarS, is an important negative regulator of the ACT and RED production in S. coelicolor. KEY POINTS: • GarR/GarS is a TCS with domains for signal transduction and response regulation • GarR/GarS is an essential negative regulator of the ACT and RED production • GarR/GarS putatively interacts with and regulates activators of ACT and RED.

[Establishment and Optimization of Quality Standards for the Traditional Tibetan Medicine Preparation of Liuwei Nengxiao Pills]. / è—è¯å ­å‘³èƒ½æ¶ˆä¸¸è´¨é‡æ ‡å‡†çš„å»ºç«‹ä¸Žä¼˜åŒ–.

Objective: To establish quality standards for Liuwei Nengxiao pills, to optimize the quality control method, and to provide references for the quality control of Liuwei Nengxiao pills. Methods: Chebula, dried ginger, and Tibetan liqueur root in Liuwei Nengxiao pills of different batch numbers were analyzed by thin layer chromatography (TLC). Then, the content of chrysophanol in the preparation was determined by high performance liquid chromatography (HPLC). Furthermore, a series of methodological validation, including the investigation of the linear relationship, precision, stability, and reproducibility and sample recovery test, were performed to verify the reliability of the results. Results: The TLC identification method was easy to perform and demonstrated high specificity, clear spots, and good separation effect. In addition, the negative controls showed no interference. The HPLC method showed high accuracy. The results of methodological validation showed that the peak area of chrysophanol had a good linear relationship (r2=1.0) in the range of 0.06-0.80 µg, presenting good precision (with the relative standard deviation being lower than 2.0%), good stability and reproducibility (with the relative standard deviation being lower than 1.0%), and an average recovery rate of 100.8%. Conclusion: TLC and HPLC are easy to perform, showing high accuracy and reproducibility. The quality standards established are scientific, reasonable, stable, and feasible, providing references for the quality control of Liuwei Nengxiao pills.

Folic Acid Functionalized AQ4N/Gd@PDA Nanoplatform with Real-Time Monitoring of Hypoxia Relief and Enhanced Synergistic Chemo/Photothermal Therapy in Glioma.

Purpose: Hypoxia is often associated with glioma chemoresistance, and alleviating hypoxia is also crucial for improving treatment efficacy. However, although there are already some methods that can improve efficacy by alleviating hypoxia, real-time monitoring that can truly achieve hypoxia relief and efficacy feedback still needs to be explored. Methods: AQ4N/Gd@PDA-FA nanoparticles (AGPF NPs) were synthesized using a one-pot method and were characterized. The effects of AGPF NPs on cell viability, cellular uptake, and apoptosis were investigated using the U87 cell line. Moreover, the effectiveness of AGPF NPs in alleviating hypoxia was explored in tumor-bearing mice through photoacoustic imaging. In addition, the diagnosis and treatment effect of AGPF NPs were evaluated by magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) on orthotopic glioma mice respectively. Results: In vitro experiments showed that AGPF NPs had good dispersion, stability, and controlled release. AGPF NPs were internalized by cells through endocytosis, and could significantly reduce the survival rate of U87 cells and increase apoptosis under irradiation. In addition, we monitored blood oxygen saturation at the tumor site in real-time through photoacoustic imaging (PAI), and the results showed that synergistic mild-photothermal therapy/chemotherapy effectively alleviated tumor hypoxia. Finally, in vivo anti-tumor experiments have shown that synergistic therapy can effectively alleviate hypoxia and inhibit the growth of orthotopic gliomas. Conclusion: This work not only provides an effective means for real-time monitoring of the dynamic feedback between tumor hypoxia relief and therapeutic efficacy, but also offers a potential approach for the clinical treatment of gliomas.

Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway.

Double cortin-like kinase 1 (DCLK1) exhibits high expression levels across various cancers, notably in human colorectal cancer (CRC). Diacerein, a clinically approved interleukin (IL)-1ß inhibitor for osteoarthritis treatment, was evaluated for its impact on CRC proliferation and migration, alongside its underlying mechanisms, through both in vitro and in vivo analyses. The study employed MTT assay, colony formation, wound healing, transwell assays, flow cytometry, and Hoechst 33342 staining to assess cell proliferation, migration, and apoptosis. Additionally, proteome microarray assay and western blotting analyses were conducted to elucidate diacerein's specific mechanism of action. Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo. Through high-throughput proteomics microarray and molecular docking studies, we identified that diacerein directly interacts with DCLK1. Mechanistically, the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed. Furthermore, diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets, including MCL-1, VEGF, and survivin, thereby inhibiting CRC progression in a mouse model, thereby inhibiting CRC progression in a mouse model.

Visualization of bone formation in sheep's middle ear by using fluorochrome sequential labelling (FSL).

One factor for the lacking integration of the middle ear stapes footplate prosthesis or the missing healing of stapes footplate fractures could be the known osteogenic inactivity. In contrast, it was recently demonstrated that titanium prostheses with an applied collagen matrix and immobilised growth factors stimulate osteoblastic activation and differentiation on the stapes footplate. Regarding those findings, the aim of this study was to evaluate the potential of bone regeneration including bone remodeling in the middle ear. Ten one-year-old female merino sheep underwent a middle ear surgery without implantation of middle ear prostheses or any other component for activating bone formation. Post-operatively, four fluorochromes (tetracycline, alizarin complexion, calcein green and xylenol orange) were administered by subcutaneous injection at different time points after surgery (1 day: tetracycline, 7 days: alizarin, 14 days: calcein, 28 days: xylenol). After 12 weeks, the temporal bones including the lateral skull base were extracted and histologically analyzed. Fluorescence microscopy analysis of the entire stapes with the oval niche, but in particular stapes footplate and the Crura stapedis revealed evidence of new bone formation. Calcein was detected in all and xylenol in 60% of the animals. In contrast, tetracycline and alizarin could only be verified in two animals. The authors were able to demonstrate the osseoregenerative potential of the middle ear, in particular of the stapes footplate, using fluorescence sequence labelling.

Anthraquinones against Cryptococcus neoformans sensu stricto: antifungal interaction, biofilm inhibition and pathogenicity in the Caenorhabditis elegans model.

Introduction. Cryptococcal biofilms have been associated with persistent infections and antifungal resistance. Therefore, strategies, such as the association of natural compounds and antifungal drugs, have been applied for the prevention of biofilm growth. Moreover, the Caenorhabditis elegans pathogenicity model has been used to investigate the capacity to inhibit the pathogenicity of Cryptococcus neoformans sensu stricto.Hypothesis. Anthraquinones and antifungals are associated with preventing C. neoformans sensu stricto biofilm formation and disrupting these communities. Antraquinones reduced the C. neoformans sensu stricto pathogenicity in the C. elegans model.Aim. This study aimed to evaluate the in vitro interaction between aloe emodin, barbaloin or chrysophanol and itraconazole or amphotericin B against growing and mature biofilms of C. neoformans sensu stricto.Methodology. Compounds and antifungal drugs were added during biofilm formation or after 72 h of growth. Then, the metabolic activity was evaluated by the MTT reduction assay, the biomass by crystal-violet staining and the biofilm morphology by confocal laser scanning microscopy. C. neoformans sensu stricto's pathogenicity was investigated using the nematode C. elegans. Finally, pathogenicity inhibition by aloe emodin, barbarloin and chrysophanol was investigated using this model.Results. Anthraquinone-antifungal combinations affected the development of biofilms with a reduction of over 60 % in metabolic activity and above 50 % in biomass. Aloe emodin and barbaloin increased the anti-biofilm activity of antifungal drugs. Chrysophanol potentiated the effect of itraconazole against C. neoformans sensu stricto biofilms. The C. elegans mortality rate reached 76.7 % after the worms were exposed to C. neoformans sensu stricto for 96 h. Aloe emodin, barbaloin and chrysophanol reduced the C. elegans pathogenicity with mortality rates of 61.12 %, 65 % and 53.34 %, respectively, after the worms were exposed for 96 h to C. neoformans sensu stricto and these compounds at same time.Conclusion. These results highlight the potential activity of anthraquinones to increase the effectiveness of antifungal drugs against cryptococcal biofilms.

Anti-inflammatory effect of luteoloside against methylglyoxal induced human dental pulp cells.

PURPOSE: The aim of this study was to investigate whether luteoloside, a flavonoid, could protect human dental pulp cells (HDPCs) against inflammation and oxidative stress induced by methylglyoxal (MGO), one of the advanced glycated end products (AGE) substances. METHODS: HDPCs were stimulated with MGO and treated with luteoloside. MTT assay was used to determine cell viability. Protein expression was measured via western blotting. Reactive oxygen species (ROS) were measured with a Muse Cell Analyzer. Alkaline phosphatase activity (ALP) and Alizarin red staining were used for mineralization assay. RESULTS: Luteoloside down-regulated the expression of inflammatory molecules such as ICAM-1, VCAM-1, TNF-α, IL-1ß, MMP-2, MMP-9, and COX-2 in MGO-induced HDPCs without showing any cytotoxicity. It attenuated ROS formation and enhanced osteogenic differentiation such as ALP activity and Alizarin red staining in MGO-induced HDPCs. Overall, luteoloside showed protective actions against inflammation and oxidative stress in HDPCs induced by MGO through its anti-inflammatory, anti-oxidative, and osteogenic activities by down-regulating p-JNK in the MAPK pathway. CONCLUSION: These results suggest that luteoloside might be a potential adjunctive therapeutic agent for treating pulpal pathological conditions in patients with diabetes mellitus.

Establishment and validation of a nomogram clinical prediction model for osteoporosis in senile patients with type 2 diabetes mellitus.

This study aimed to develop a predictive nomogram model to estimate the odds of osteoporosis (OP) in elderly patients with type 2 diabetes mellitus (T2DM) and validate its prediction efficiency. The hospitalized elderly patients with T2DM from the Affiliated Hospital of North Sichuan Medical University between July 2022 and March 2023 were included in this study. We sorted them into the model group and the validation group with a ratio of 7:3 randomly. The selection operator regression (LASSO) algorithm was utilized to select the optimal matching factors, which were then included in a multifactorial forward stepwise logistic regression to determine independent influencing factors and develop a nomogram. The discrimination, accuracy, and clinical efficacy of the nomogram model were analyzed utilizing the receiver operating characteristic (ROC) curve, calibration curve, and clinical decision curve analysis (DCA). A total of 379 study participants were included in this study. Gender (OR = 8.801, 95% CI 4.695-16.499), Geriatric Nutritional Risk Index (GNRI) < 98 (OR = 4.698, 95% CI 2.416-9.135), serum calcium (Ca) (OR = 0.023, 95% CI 0.003-0.154), glycated hemoglobin (HbA1c) (OR = 1.181, 95% CI 1.055-1.322), duration of diabetes (OR = 1.076, 95% CI 1.034-1.119), and serum creatinine (SCr) (OR = 0.984, 95% CI 0.975-0.993) were identified as independent influencing factors for DOP occurrence in the elderly. The area under the curve (AUC) of the nomogram model was 0.844 (95% CI 0.797-0.89) in the modeling group and 0.878 (95% CI 0.814-0.942) in the validation group. The nomogram clinical prediction model was well generalized and had moderate predictive value (AUC > 0.7), better calibration, and better clinical benefit. The nomogram model established in this study has good discrimination and accuracy, allowing for intuitive and individualized analysis of the risk of DOP occurrence in elderly individuals. It can identify high-risk populations and facilitate the development of effective preventive measures.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin.

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

Metabolomics analysis reveals the metabolite profiles of Rheum tanguticum grown under different altitudinal gradients.

BACKGROUND: Plant growth and quality are often affected by environmental factors, including geographical location, climate, and soil. In this study, we describe the effect of altitudinal differences on the growth and active ingredients in Rheum tanguticum Maxim. ex Balf. (R. tanguticum), a traditional Chinese medicinal herb known for its laxative properties. RESULTS: The results showed that plants grown at lower altitudes had better growth performances than those in higher altitude areas. The yield varied by 2.45-23.68 times with altitude, reaching a maximum of 102.01 t/ha. In addition, total anthraquinone and total sennoside contents decreased with increasing altitude, whereas total tannins increased with increasing altitude. The total anthraquinone content of the indicator compound reached 5.15% at five experimental sites, which exceeded the Chinese Pharmacopoeia standard by 70.87%. The content of the other two categories of active ingredients reached a maximum value of 0.94% (total sennosides) and 2.65% (total tannins). Redundancy analysis revealed that annual rainfall, annual average temperature, annual sunshine hours, and pH significantly affected growth and active ingredients. Moreover, key metabolites, such as flavonoids, amino acids and their derivatives, phenolic acids, lipids, and terpenes, were differentially expressed between samples from low- and high-altitude cultivation areas. These metabolites were enriched in the flavonoid and flavonol biosynthetic pathway and the monoterpene biosynthetic pathway. CONCLUSIONS: These results suggest that high anthraquinone content was observed in the lowest-latitude cultivation area due to low rainfall and alkaline soil pH. Key metabolites were significantly upregulated in high-latitude cultivation areas. These results provide a scientific basis for quality control and the systematic cultivation of R. tanguticum.

Novel Anthraquinone-Based Benzenesulfonamide Derivatives and Their Analogues as Potent Human Carbonic Anhydrase Inhibitors with Antitumor Activity: Synthesis, Biological Evaluation, and In Silico Analysis.

In this study, we designed two series of novel anthraquinone-based benzenesulfonamide derivatives and their analogues as potential carbonic anhydrase inhibitors (CAIs) and evaluated their inhibitory activities against off-target human carbonic anhydrase II (hCA II) isoform and tumor-associated human carbonic anhydrase IX (hCA IX) isoform. Most of these compounds exhibited good inhibitory activities against hCA II and IX. The compounds that exhibited the best hCA inhibition were further studied against the MDA-MB-231, MCF-7, and HepG2 cell lines under hypoxic and normoxic conditions. Additionally, the compounds exhibiting the best antitumor activity were subjected to apoptosis and mitochondrial membrane potential assays, which revealed a significant increase in the percentage of apoptotic cells and a notable decrease in cell viability. Molecular docking studies were performed to demonstrate the presence of numerous hydrogen bonds and hydrophobic interactions between the compounds and the active site of hCA. Absorption, distribution, metabolism, excretion (ADME) predictions showed that all of the compounds had good pharmacokinetic and physicochemical properties.

A comprehensive review of Pfaffia glomerata botany, ethnopharmacology, phytochemistry, biological activities, and biotechnology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng.) Pedersen, Amaranthaceae, is found in South America, mainly in Brazil, where it is considered a species of great medicinal interest owing to its popular use as a tonic, aphrodisiac, anti-inflammatory, and analgesic. These properties can be attributed to the presence of the phytosteroid, 20-Hydroxyecdysone (ß-ecdysone), the main compound found in its roots. AIM OF THE REVIEW: This review aims to provide information about the botanical characteristics, ethnomedicinal uses, the phytochemistry, the biological activities, and the biotechnology of P. glomerata, an important species to local communities and groups researching medicinal plants of South America. MATERIALS AND METHODS: The information available on P. glomerata was collected from scientific databases (ScienceDirect, PubMed/MEDLINE, SciELO, and Scopus) until June 7, 2023, using the search terms "Pfaffia glomerata", "Pfaffia glomerata (Spreng.) Pedersen", and "Brazilian ginseng". The review includes studies that evaluated the botanical, ethnopharmacological, and phytochemical aspects, biological properties, nutraceutical uses, and the application of biotechnology for improving the biosynthesis of metabolites of interest. RESULTS: A total of 207 studies were identified, with 81 articles read in full. Seventy-six studies were included for qualitative synthesis. Overall, 40 compounds belonging to different classes are presented in this review, including ecdysteroids, triterpenes, saponins, flavonoids, anthraquinones, tannins, coumarins, alkaloids, and polysaccharides. Among them, flavonoids, anthraquinones, tannins, coumarins, and alkaloids were only putatively identified. ß-Ecdysone, triterpenes, saponins, and polysaccharides are the chemical components most frequently identified and isolated from P. glomerata and possibly responsible for ethnopharmacological use and the biological activities of this species, with important in vitro and in vivo activities, such as anti-inflammatory, antidepressant, aphrodisiac, analgesic, gastroprotective, antioxidant, and prebiotic. CONCLUSIONS: This review summarizes discussions about the P. glomerata species, highlighting its ethnopharmacological, chemical, biotechnological, and nutraceutical importance. New scientific studies on this species are encouraged in the search for new therapeutic molecules with pharmaceutical potential and nutraceutical applications.

Innovative modification of cellulose fibers for paper-based electrode materials using metal-organic coordination polymers.

Cellulosic paper-based electrode materials have attracted increasing attention in the field of flexible supercapacitor. As a conductive polymer, polyaniline exhibits high theoretical pseudocapacitive capacitance and has been applied in paper-based electrode materials along with cellulose fibers. However, the stacking of polyaniline usually leads to poor performance of electrodes. In this study, metal-organic coordination polymers of zirconium-alizarin red S and zirconium-phytic acid are applied to modulate the polyaniline layer to obtain high-performance cellulosic paper-based electrode materials. Zirconium hydroxide is firstly loaded on cellulose fibers while alizarin red S and phytic acid are introduced to regulate the morphology of polyaniline through doping and coordination processes. The results show that the introduction of dual coordination polymers is effective to regulate the morphology of polyaniline on cellulose fibers. The performances of the paper-based electrode materials, including electrical conductivity and electrochemistry, are apparently improved. It provides a promising strategy for the potential development of economical and green electrode materials in the conventional paper-making process.