Journal of Holistic Integrative Pharmacy最新文献

Objective

Methods

Results

Conclusion

Objective

Methods

Results

Conclusion

Objective

Currently, the incidence of hepatocellular carcinoma remains high, and the prognosis of patients is poor. Prognostic biomarkers are still worth exploring.

Methods

Based on The Cancer Genome Atlas (TCGA) database, the differentially expressed genes (DEGs) were screened. Subsequently, a modular analysis of these DEGs was performed using the weighted gene co-expression network analysis (WGCNA). A prognostic model for liver cancer patients was constructed employing the Cox proportional hazards model. Through univariate and multivariate Cox regression analyses, we developed a Cox proportional-hazards model specifically for hepatocellular carcinoma. Subsequently, International Cancer Genome Consortium (ICGC) cohort data were used to validate the accuracy of the Cox proportional-hazards model. Following this, we conducted further analyses of prognostic genes, encompassing functional enrichment analysis and survival analysis. Additionally, we utilized the BBcancer database to investigate whether these prognostic genes have the potential to serve as blood markers. Notably, in this six-gene prognostic model, we also analyzed the genes' drug susceptibility.

Results

Leveraging the candidate genes identified from the WGCNA analysis, we constructed a Cox proportional-hazards model with an AUC value greater than 0.7. This model incorporates HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1, revealing that patients with low expression levels of these genes had significantly better survival prognosis compared to those with high expression levels (P ​< ​0.05). The enrichment analysis revealed that these prognostic genes are enriched in pathways related to hepatitis B, hepatitis C, and hepatocellular carcinoma. Furthermore, we observed a strong association between HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1 with overall survival (OS) in hepatocellular carcinoma (HCC) patients, among which HMMR, E2F2, WDR62 and KIF11 genes were significantly differentially expressed in extracellular vesicles. Additionally, this six-gene prognostic model demonstrated sensitivity to drugs such as VX-680, TAE684, Sunitinib, S-Trityl-L-cysteine, Paclitaxel, and CGP-60474.

Conclusion

The Cox risk prognostic model based on HMMR, E2F2, WDR62, KIF11, MSH4, and KCNF1 represents a valuable tool for predicting the prognosis of HCC patients and may serve as a target for drug development. In particular, HMMR, E2F2, WDR62, and KIF11 have potential as blood biomarkers for hepatocellular carcinoma, though their precise biological functions require further exploration.

In traditional Chinese medicine (TCM), the kidney is considered the "innate foundation", and the abundance or diminution of its essence directly affects the growth, development, physical form, and physiological functions of the human body. As people reach middle age and old age, the essence in the kidney gradually decreases, and the signs of aging become more apparent. Immune aging is a common phenomenon in life, characterized by quantitative or functional changes in cells and molecules within the immune system. It is one of the main causes of organ aging, leading to increased inflammation, decreased immune regulatory capacity and declining organ function. TCM has a rich clinical practice and pharmacological research supporting its efficacy in delaying aging. This review focuses on Chinese medicine and formulas that tonify kidney yang and kidney yin, with the goal of delaying aging by regulating immune mechanisms. It provides a theoretical basis for understanding the role of TCM in anti-aging and prevention of senescence, as well as guiding the development of new products, theories, and directions in anti-aging research.

Objective

There is a scarcity of transcriptome sequencing data available for the Leptopetalum biflorum, and numerous cyclotides remain undiscovered. It is urgent to establish a workflow based on de novo transcriptome assembly and make systematic prediction of cyclotides in Leptopetalum biflorum, to provide a reference for functional analysis of cyclotides.

Methods

In this study, we performed RNA-seq on roots, leaves, and flowers of Leptopetalum biflorum to obtain two sets of transcriptome data. The quality assessment of the sequencing was conducted using FastQC and MultiQC. De novo transcriptome assembly of Leptopetalum biflorum was carried out using Trinity, with assembly quality evaluated through the Read Support method and BUSCO tool analysis. The eggnog-mapper and Trinotate were used to annotate functional terms in GO and pathways in KEGG. The Transdecoder was utilized to predict ORFs and coding regions while SignalP software was employed to predict amino acid sequences containing signal peptides and signal peptide splicing sites. The mature protein sequences are subsequently used for cyclotide prediction in Leptopetalum biflorum via FindCRP 2.0 (Find Cyclotide Peptide), a cyclotide prediction tool developed by our team.

Results

Trinity assembled a total of 171,310 transcripts and 103,299 isoforms (genes). The average transcript length was 1139.89, while the average gene length was 780.87. Approximately 30% of the genes exhibited homology within other plant species. Among these genes, 23,265 (22.52%) were annotated into 41 GO terms at Level 2. The KEGG pathway annotation revealed that 23,682 genes (22.92%) contained 5171 KO annotations and were involved in 484 pathways. FindCRP predicted 17 potential cyclotides, among which 15 sequences had homologous genes; notably five potential cyclotides showed complete identity (100%) to their respective homologous genes. Additionally, two potential cyclotide sequences without any identified homologous demonstrated circle-forming ability based on the 3D structure prediction results.

Conclusion

In this study, we developed a de novo transcriptome assembly workflow for the identification of cyclotides using RNA-seq data from Leptopetalum biflorum. Our custom-built tool, FindCRP, was employed in this workflow to detect potential cyclotides. This meticulously designed workflow ensures the reproducibility and reliability of our study findings. We successfully performed transcript annotation and predicted putative cyclotides. These potential cyclotides show significant homology to known cyclotides.

Objective

To investigate the anti-inflammatory properties of Qingjie Fuzheng granules (QFG) in vivo using a dextran sulfate sodium (DSS)–induced ulcerative colitis (UC) model and elucidate the mechanism of which QFG alleviates UC by examining T cell 17 (Th17)/regulatory T cell (Treg) balance.

Methods

The DSS-induced UC murine model was established, and the mice were administered QFG or saline by gavage. Their general growth characteristics, including body weight, fecal occult blood, and disease activity index were observed, and the length of the colon was recorded. Hematoxylin and eosin staining was performed to examine pathological injury within the colon tissue. The expression levels of Th17-related cytokines, Treg-related cytokines, interferon-γ (IFN-γ), indoleamine 2,3-dioxygenase 1 (IDO1), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the serum were detected by enzyme-linked immunosorbent assay or Bio-Plex immunoassay. Relative mRNA expressions in the spleen and colon tissues were detected by reverse transcription–quantitative polymerase chain reaction. The protein expressions of retinoic acid–associated orphan receptor γt (RORγt), Forked head/wing helix transcription factor 3 (Foxp3), or IDO1 were detected in the spleen and colon by western blotting or immunohistochemistry.

Results

QFG demonstrated the potential to improve the overall pathological conditions of DSS-induced UC mice as evidenced by significantly alleviating the colon shortening and improving colon tissue pathology. QFG also decreased expressions of the pro-inflammatory cytokines IL-1β, TNF-α, IFN-γ, and interleukin-6 as well as IDO1. QFG treatment significantly reduced the expressions of Th17-related cytokines and concurrently increased the expressions of Treg-related cytokines. After QFG treatment, the expression of transcription factor RORγt decreased in the colon and spleen, while that of the transcription factor Foxp3 increased.

Conclusion

QFG can suppress inflammation in mice with DSS-induced UC. This effect is achieved through the regulation of transcription factors RORγt and Foxp3, which inhibits Th17 ​cell differentiation, promotes Treg cell differentiation, and maintains Th17/Treg balance.

Rheumatic immune disorders are a group of conditions that affect the immune system, leading to various clinical symptoms. These diseases can cause pain, reduce the quality of life, and increase the risk of death in severe cases. Diagnosis and treatment are very complex due to the different types of disease and individual differences and the unknown pathogenesis of the disease. Further research is necessary to provide new clues for disease treatment. Organoid technology that makes up for the shortcomings of animal model species differences can better simulate disease onset mechanisms than animal models. It can be used as a screening platform for new therapeutic targets, as well as personalized settings based on patient-derived organoids, promising as an effective tool for the study of rheumatic immune diseases. Therefore, the article summarizes studies related to organoids and their application in rheumatic immune diseases. It also provides an outlook on the potential of organoids in this field and discusses the challenges that need to be addressed, putting new ideas for future research on these diseases.

The purpose of this study was to explore the relationship between the evolution of key Salvia enzyme genes and metabolite biological activity on mitochondrial quality control. Metabolomics and transcriptomics were performed to detect the metabolites of Salvia and 76AH1 (CYP450) genes and a maximum likelihood tree for Salvia was established. Additionally, the protein properties of 76AH were analyzed and the metabolite, as well as mitochondrial quality control, targets were downloaded from the TCMSP, BATMAN, and GeneCards databases and analyzed. Molecular docking of PINK1 with cryptotanshinone and tanshinone IIA was assessed and a molecular binding area was identified. Moreover, the specific types of Salvia secondary metabolites were accurately identified and quantified with nearly all AH1 genes having been sequenced. This study begins to elucidate the relationship between species evolution and biological activity. Specifically, the structural analysis demonstrates that cryptotanshinone and tanshinone IIA exhibit strong pharmacological activity in mitochondrial quality control.

Exosomes are nanoparticles that can be secreted by almost all cells into the extracellular space and carry active substances such as nucleic acids, lipids, and proteins and can participate in intercellular signaling. Exosomes are consequently used as a natural medicinal ingredient and can also play a role as carriers of biomarkers and drugs. The heterogeneous nature of exosomes suggests that they have considerable potential for diagnosing and treating multiple diseases. However, standardized methods for exosome isolation are still lacking to ensure the yield, purity, and quality of exosomes, which consequently limits their applications. Therefore, isolation methods that produce exosomes with a high yield, purity, and stability and are supported by standardized characterization techniques need to be further developed. In 2018, the International Society for Extracellular Vesicles released guidelines for the isolation and characterization standards of exosomes, and in this review, we have prepared a comprehensive discussion based on these guidelines that describes the biogenesis of exosomes and the principles, advantages, disadvantages, and application prospects of their isolation techniques to provide basic information for the study of exosomes.

Background and aim

Liujunzi Decoction (LJZD), also called Rikkunshito, is a traditional formula that has proven effective in clinical treatment against chemotherapy-induced anorexia (CIA). Previous study indicated the importance of GDF15/GFRAL axis in the pathogenesis of CIA, and suggested the potential connection between endoplasmic reticulum stress and GDF15 expression. However, further exploration is required to determine whether the mechanism of LJZD against CIA is related to the PERK/eIF2α/ATF4/CHOP signaling and GDF15/GFRAL expression.

Methods

The CIA model of rats was established via intraperitoneal injection of cisplatin, and the rats were given LJZD orally for 72 ​h. Food intake and body weight were recorded daily. The expression of GDF15/GFRAL and ER stress factors, as well as the histological injuries were investigated.

Results

LJZD led to a significant increase in food intake in rats and a decrease in serum GDF15 levels at 24 ​h and 72 ​h after cisplatin injection. This effect may be associated with the inhibition of Gdf15 transcription and the amelioration of pathological injuries or endoplasmic reticulum stress in the liver and ileum. Moreover, LJZD suppressed the cisplatin-induced activation of the hepatic and ileal PERK/eIF2α/ATF4/CHOP pathway, resulting in the alleviation of central GDF15/GFRAL expression.

Conclusion

LJZD effectively improves cisplatin-induced anorexia in a rat model, which might be attributed to its inhibition of the PERK/eIF2α/ATF4/CHOP pathway and GDF15/GFRAL expression activated by cisplatin.