To investigate the antioxidative mechanism of snake venom-derived protein C activator (PCA) in mitigating vascular endothelial cell injury.

Soil cadmium (Cd) pollution is one of the major environmental problems globally. Ophiopogon japonicus, a multifunctional plant extensively used in traditional Chinese medicine, has demonstrated potential in environmental remediation. This study investigated the Cd accumulation pattern of O. japonicus under cadmium stress and identified the heavy metal ATPase (HMA) family members in this plant. Our results demonstrated that O. japonicus exhibited a Cd enrichment factor (EF) of 2.75, demonstrating strong potential for soil Cd pollution remediation. Nine heavy metal ATPase (HMA) members of P1B-ATPases were successfully identified from the transcriptome data of O. japonicus, with OjHMA1-OjHMA6 classified as the Zn/Co/Cd/Pb-ATPases and OjHMA7-OjHMA9 as the Cu/Ag-ATPases. The expression levels of OjHMA1, OjHMA2, OjHMA3, and OjHMA7 were significantly up-regulated under Cd stress, highlighting their crucial roles in cadmium ion absorption and transport. The topological analysis revealed that these proteins possessed characteristic transmembrane (TM) segments of the family, along with functional A, P, and N domains involved in regulating ion absorption and release. Metal ion-binding sites (M4, M5, and M6) existed on the TM segments. Based on the number of transmembrane domains and the residues at metal ion-binding sites, the plant HMA family members were categorized into three subgroups: P1B-1 ATPases, P1B-2 ATPases, and P1B-4 ATPases. Specifically, the P1B-1 ATPase subgroup included the motifs TM4(CPC), TM5(YN[X]4P), and TM6(M[XX]SS); the P1B-2 ATPase subgroup featured the motifs TM4(CPC), TM5(K), and TM6(DKTGT); the P1B-4 ATPase subgroup contained the motifs TM4(SPC) and TM6(HE[X]GT), all of which were critical for protein functions. Molecular docking results revealed the importance of conserved sequences such as CPC/SPC, DKTGT, and HE[X]GT in metal ion coordination and stabilization. These findings provide potential molecular targets for enhancing Cd uptake and tolerance of O. japonicus by genetic engineering and lay a theoretical foundation for developing new cultivars with high Cd accumulation capacity.

Ophiopogon japonicus, a precious medicinal plant endemic to Zhejiang Province. Its tuberous roots are rich in bioactive components such as flavonoids, possessing anti-inflammatory, antioxidant, and immunomodulatory properties. To elucidate the impact of cadmium (Cd) stress on the accumulation and biosynthetic pathway of flavonoids in O. japonicus, this study exposed O. japonicus to different concentrations of Cd stress and explored the changes through integrated transcriptomics and metabolomics analysis. The results demonstrated that Cd stress (1 mg/L and 10 mg/L) significantly increased the content of flavonoids in O. japonicus in a concentration-dependent manner. The metabolomics analysis revealed a total of 110 flavonoids including flavones, flavanols, flavonols, flavone and flavonol derivatives, flavanones, isoflavonoids, chalcones and dihydrochalcones, and anthocyanins in O. japonicus, among which flavones, flavonols, flavone and flavonol derivatives, and anthocyanins increased under Cd stress. The transcriptomics analysis identified several key flavonoid biosynthesis-associated genes with up-regulated expression under Cd stress, including 14 genes encoding 4-coumarate CoA ligase (4CL), 2 genes encoding chalcone isomerase (CHI), and 14 genes encoding phenylalanine ammonia lyase (PAL). The gene-metabolite regulatory network indicated significant positive correlations of 4CL (Cluster-21637.5012, Cluster-21637.90648, and Cluster-21637.62637) and CHI (Cluster-21637.111909 and Cluster-21637.123300) with flavonoid metabolites, suggesting that these genes promoted the synthesis of specific flavonoid metabolites, which led to the accumulation of total flavonoids under Cd stress. These findings provide theoretical support for the cultivation and utilization of medicinal plants in Cd-contaminated environments and offered new perspectives for studying plant responses to heavy metal stress.

To investigate the expression of Acyl-CoA synthetase long-chain family member 4 (ACSL4) in liver cancer and its role in regulating ferroptosis and proliferation of liver cancer cells.

To explore the potential role and mechanism of compound tetramethylpyrazine in gastric cancer therapy by using network pharmacology analysis combined with gene function annotation and clinical data analysis.

Terpene synthases (TPSs) play a crucial role in the synthesis of terpenoids that contribute to the scent profiles of flowers. However, few studies report the genome-wide analysis of TPSs gene in Jasminum sambac var. Fuzhou bifoliatum and their expression pattern in response to methyl jasmonate (MeJA). In this study, we employed bioinformatics tools for genome-wide analysis of the J. sambac TPS (DJTPS) gene family and determined the physical and chemical properties, subcellular location, protein-protein interactions, phylogenetic relationship, subfamily classification, chromosomal location and collinearity, gene structure, conserved motifs, and promoter cis-acting elements. The expression patterns of DJTPSs in different tissues and in response to MeJA treatment were analyzed based on the transcriptome data combined with quantitative real-time PCR (qRT-PCR). We identified 32 intact DJTPS genes in the genome of J. sambac, which presented uneven distribution across nine chromosomes. All the deduced proteins were hydrophilic, predominantly localized in the cytoplasm. The phylogenetic analysis classified the DJTPS genes into five subfamilies: TPS-a, TPS-b, TPS-c, TPS-e/f, and TPS-g. The results of the collinearity analysis showed a total of 10 sets of replication events in DJTPSs, most of which underwent purifying selection. A comparative analysis of TPS homologous gene pairs was performed among J. sambac var. Fuzhou bifoliatum and other six species, which revealed different number of homologous gene pairs. The number of exons and motifs was conserved within the same subfamily. DJTPS genes carried multiple elements that may be involved in the response to MeJA. In addition, the transcriptome and qRT-PCR data unveiled that several TPS genes exhibited tissue-specific expression patterns, and the genes with specific expression in flowers were the most. Upon exposure to MeJA, 14 TPS genes showcased upregulated expression 5 h or 6 h post-treatment, and DJTPS03, DJTPS04 and DJTPS21 showed significantly increased expression levels after MeJA treatment. This study provides preliminary evidence that MeJA possesses the ability to enhance the expression of DJTPS genes during the critical flowering stage, which will facilitate the synthesis of terpenoids and improve the quality of floral fragrance.

Ovarian cancer is a serious threat to women's health and safety. So far, people have discovered more than 130 small molecule compounds of natural origin for anti-tumor, of which approximately 50% are of microbial origin. The Acanthus ilicifolius L. species is primarily distributed in the Guangdong, Hainan, and Guangxi regions of China and grows in tidally accessible coastal areas. Recent studies have revealed that Acanthus ilicifolius L. extracts are endowed with a range of pharmacological properties, including anti-inflammatory, hepatoprotective, antioxidant, and antitumor activities. Endophytic fungi are commonly found in the healthy tissue and organs of medicinal plants. These fungi and the plants they inhabit form mutually beneficial symbiotic relationships. Endophytic fungi produce a series of secondary metabolites, with active substances having shown great economic value and applications prospects in drug research and development as well as for the biological control of plant diseases. Secondary metabolites production by endophytic fungi is regulated by specific gene clusters, and several techniques have been used to stimulate the secondary metabolic processes of fungi, including epigenetic-modification and OSMAC (one strain many compounds) strategies, co-culturing, and gene modification. Among these, epigenetic modification has been shown to be effective; this strategy involves the addition of small-molecule epigenetic modifiers to the culture medium, thereby activating silenced biosynthetic gene clusters without altering the DNA sequences of the fungi. This approach facilitates the expression of silenced genes in endophytic fungi, thereby increasing the number and diversity of secondary metabolites. Furthermore, it assists in overcoming the inhibition of microbial secondary-metabolite synthesis under laboratory conditions, and enhances silenced-gene expressions. The advent of novel analytical techniques and bioinformatics has provided a comprehensive, multifaceted, and holistic understanding of fungal metabolism through the development of metabolomics as a research platform. However, few studies have combined anti-ovarian cancer-activity screening with metabolomic approaches in the search for activity-differentiating metabolites from endophytic fungi under the intervention of epigenetic modifiers. Herein, we investigated the impact of epigenetic modifiers on the secondary metabolites of the endophytic Diaporthe goulteri fungus from Acanthus ilicifolius L. to determine their potential anti-ovarian cancer activities. Crude extracts were obtained by controlling three variables: the number of fermentation days, the type of epigenetic modifier, and its concentration, with activities screened using the CCK-8 (cell counting kit-8) method. Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was subsequently employed for non-targeted metabolomic analysis. A multivariate statistical analysis model was constructed using principal component analysis and orthogonal partial least squares-discriminant analysis, which combines model and variable importance projection, with qualitative screening performed and significant changes (variable importance in the projection (VIP)≥1; P<0. 05) determined. Fifteen differential metabolites were identified in the fungal and epigenetic modification group, primarily comprising polyketides, amino acids, derivatives, alkaloids, and organic acids, including prenderol, glycine, valine, 2-ethylcaproic acid, rubratoxin B, finasteride, 6-silaspiro[5.5]undecane, 1-(2-nitrophenoxy)octane, heptadecene, 1-pentadecene, 11-ketoetiocholanolone, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, tabutrex, (3aR,6S,6aS)-6-(4-hydroxy-2-methoxy-2-butanyl)-4,4-dimethylhexahydro-1(2H)-pentalenone, and 8-aminoquinoline. The expressions of prenderol, 1-(2-nitrophenoxy)octane, 3-(1-ethyl-1,3,3-trimethyl-2,3-dihydro-1H-inden-5-yl)butanal, N2-benzoylarginine, and 8-aminoquinoline were downregulated, whereas the expressions of the remaining 10 substances were upregulated. Polyketides were the main components that exhibited higher expressions. This study showed that latent active differential metabolites can be searched by combining anti-ovarian cancer-activity screening with metabolomics analysis, thereby providing a reference for the further development of Acanthus ilicifolius L. resources and the subsequent targeted isolation of active compounds.

To investigate the effect of sanguinarine (SAN) on proliferation and ferroptosis of colorectal cancer cells.

With the rapid development of traditional Chinese medicine and the continuous discovery of various anticancer effects of salidroside (sal), it is known that sal inhibits tumor proliferation, invasion and migration by inducing apoptosis and autophagy, regulating the cell cycle, modulating the tumor microenvironment, and controlling cancer-related signaling pathways and molecules. The microRNA (miRNA)-mRNA signaling axis can regulate the expression of target mRNAs by altering miRNA expression, thereby affecting the growth cycle, proliferation, and metabolism of cancer cells. Studies have shown that sal can influence the occurrence and progression of various malignant tumors through the miRNA-mRNA signaling axis, inhibiting the progression of lung cancer, gastric cancer, and nasopharyngeal carcinoma, with a notable time and dose dependence in its antitumor effects. Summarizing the specific mechanism of sal regulating miRNA-mRNA signaling axis to inhibit tumors in recent years can provide a new theoretical basis, diagnosis, and therapeutic methods for the research on prevention and treatment of tumors.

To investigate the molecular mechanism through which calenduloside E inhibits hepatocellular carcinoma (HCC) cell proliferation and migration.

This study aims to explore the roles of three estrogen receptors (Esr1, Esr2, and Gper1) in early differentiation of embryonic gonads of Trachemys scripta. The expression characteristics of the receptor genes were studied first. The Esr1, Esr2, and Gper1 agonists PPT, WAY 200070, and G-1 were respectively injected into the embryos at the male-producing temperature (MPT) before initiation of gonadal differentiation. The sex reversal of the treated embryonic gonads was analyzed in terms of morphological structure of gonads, distribution pattern of germ cells, and expression of key genes and proteins involved in sex differentiation. The expression level of esr1 during the critical stage of sex differentiation was higher than those of esr2 and gper1 (very low expression) and was particularly high in the gonads at the female-producing temperature (FPT). After treatment with PPT, the MPT gonads presented obviously feminized morphology and structure, with the germ cells exhibiting a female distribution pattern. Furthermore, the mRNA expression levels of the key genes (dmrt1, amh, and sox9) for male differentiation were down-regulated significantly, while those of the key genes (foxl2 and cyp19a1) for female differentiation were up-regulated observably. The fluorescent signals of Amh and Sox9 expression almost disappeared, while Foxl2 and Arom were activated to express abundantly, which fully demonstrated the sex reversal of the gonads from male to female (sex reversal rate: 70.27%). However, the MPT gonads treated with WAY 200070 and G-1 still differentiated into testes, and the expression patterns of the key genes and proteins were similar to those in male gonads. The above results demonstrate that activation of Esr1 alone can fully initiate the early female differentiation process of gonads, suggesting that estrogen may induce early ovarian differentiation via Esr1 in Trachemys scripta. The findings provide a basis for further revealing the mechanisms of estrogen regulation in sex determination and differentiation of turtles.

Super-enhancer-associated genes may be closely related to the progression of osteosarcoma, curcumin exhibits a certain inhibitory effect on tumors such as osteosarcoma. This study aims to investigate the effects of curcumin on osteosarcoma in vitro and in vivo, and to determine whether curcumin can inhibit the progression of osteosarcoma by suppressing the expression of super-enhancer-associated genes LIM and senescent cell antigen-like-containing domain 1 (LIMS1), secreted protein acidic and rich in cysteine (SPARC), and sterile alpha motif domain containing 4A (SAMD4A).

To investigate the effect of Sanshentongmai (SSTM) mixture on the regulation of oxidative damage to rat cardiomyocytes (H9C2) through microRNA-146a and its mechanism.

To explore the neuroprotective effect of coenzyme Q10 and its possible mechanism in mice with chronic restraint stress (CRS).

To explore the inhibitory effect of Sidaxue, a traditional Miao herbal medicine formula, on articular bone and cartilage destruction and synovial neovascularization in rats with collagen-induced arthritis (CIA).

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3:03±0:59 vs.2:42±0:37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusion Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

To explore the mechanism by which estradiol modulates the immunophenotype of macrophages through the endoplasmic reticulum stress pathway.

To assess the inhibitory effects of aloin on lactate-induced gastric proliferation and migration of cancer cells and explore the underlying molecular mechanism.

Immunotherapy is one of the main strategies of anti-tumor therapy at present, in which immune checkpoint inhibitors (ICIs) are the most widely used drug. ICIs resistance is mediated by a variety of cytokines and immune cells, and the mechanism is complex, which is the main reason for the failure of immunotherapy in cancer patients. Histone deacetylase inhibitor (HDACi), as a class of epigenetic regulatory drugs, plays an important role in regulating cell cycle, proliferation, differentiation, and activity. In recent years, Studies have found that HDACi can not only regulate cell biological characteristics, but also closely related to the improvement of tumor ICIs drug resistance. Therefore, the study on how HDACi enhances the efficacy of ICIs is of great significance to tumor immunotherapy. This article will review the research progress of HDACi combined with ICIs in treating malignant tumors and their related mechanism.
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To investigate the regulatory effect of iridoid glycoside of radix scrophulariae (IGRS) on endoplasmic reticulum stress induced by oxygen-glucose deprivation and reperfusion in vitro model.