Journal of Holistic Integrative Pharmacy最新文献

Peptides (or polypeptides) are generally defined as those molecules compounded with less than 100 amino acids linked by peptide bonds, and the relative molecular weight is less than 10 000 Da usually. To date, more than 7 000 naturally peptides have been identified, and they play critical roles in mammalian pathophysiology. Peptide drugs are a unique kind of pharmaceutical compounds due to their different biochemical and therapeutic characteristics. This review will briefly introduce the application of peptide drugs in the treatment of common metabolic diseases and available discovery strategies for potential peptide drugs.

Background and objective

Flavonoids are important botanical metabolites, which not only protect plants from harm but also exhibit a variety of biological activities. The aim of this study was to examine the transcriptomic profiles of Abrus cantoniensis (AC) and determine the differentially expressed genes (DEGs) of flavonoids in the roots (AC-R), stems (AC-S), mature leaves (AC-ML), and tender leaves (AC-TL) of this medicinal plant.

Methods

Illumina sequencing technology was applied to sequence the transcriptome of AC. Bioinformatics tools were used to perform the de novo assembly, genes annotation, cluster analysis.

Results

More than 99.70% clean reads with 57 325 assembled unigenes were obtained. A total of 36 947 unigenes (64.45%) were successfully annotated in the Nr, SwissProt, KOG, and KEGG databases; 8 269 unigenes were assigned to 132 pathways in the KEGG database. Differential gene analysis revealed meaningful differences in the number of up- and down-regulated genes among the different parts of AC, except between AC-R and AC-S. Cluster analysis of the expression patterns of the DEGs revealed different expression trends for 20 profiles among which 9 were remarkably enriched. The most obvious difference in gene expression among AC-R, AC-S, AC-ML, and AC-TL with respect to the biosynthesis of phenylpropanoids was detected upstream in the flavonoid metabolic pathway.

Conclusion

This is the first study to provide information about the transcriptome profiles of AC and the DEGs of the flavonoid pathway in this plant.

Objective

To analyze the differential expression and prognostic value of Mitochondrial ribosomal protein L52 (MRPL52) in hepatocellular carcinoma using bioinformatics, and to explore the prognostic value and role of the MRPL52 in the immune regulation of hepatocellular carcinoma.

Methods

Hepatocellular Carcinoma Database (HCCDB) and Tumor Immune Estimation Resource (TIMER) databases were used in analyzing the differential expression of MRPL52 in hepatocellular carcinoma tissue and normal paracancerous tissues; UALCAN database was used to analyze the correlation between levels of MRPL52 expression and levels of DNA methylation vs. clinical phenotypes, including tumor grade, tumor stage, and metastasis, Kaplan–Meier plotter database was used in analyzing the relationship between MRPL52 expression and hepatocellular carcinoma survival; LinkedOmics database was used in analyzing MRPL52 co-expression genes, target miRNAs and transcription factors; GENEMANIA database was used to construct the protein interaction network; DiseaseMeth database and MEXPRESS database were used to analyze the level of MRPL52 DNA methylation and changes in methylation sites, and TIMER database was used in analyzing the relationship between MRPL52 and immune infiltration of hepatocellular carcinoma.

Results

MRPL52 was highly expressed in hepatocellular carcinoma and was positively correlated with clinical phenotypes, including tumor grade, tumor stage, and distant metastasis; high expression of MRPL52 was associated with poor prognosis of hepatocellular carcinoma; co-expression analysis showed that MRPL52 co-expression genes were enriched in multiple cancer-related signal pathways, and methylation analysis showed that the DNA methylation level of MRPL52 reduced significantly in hepatocellular carcinoma. Additionally, significant changes were found in methylation sites cg07436208 and cg04556361, which were negatively correlated with the expression level of MRPL52, and K–M survival analysis showed that the cg04556361 methylation site was negatively correlated with the overall survival of hepatocellular carcinoma; MRPL52 was associated with immune cell infiltration of hepatocellular carcinoma, and Cox multivariate regression analysis showed that MRPL52 could increase the risk of overall survival (OS) by 1.435-fold in the absence of immune cells.

Conclusion

The expression level of MRPL52 in patients with hepatocellular carcinoma is increased, which is related closely to poor prognosis, suggesting that MRPL52 is expected to become a prognostic marker and a new target for the treatment of hepatocellular carcinoma.

Abstract

Cancer-induced bone pain (CIBP) is a severe, intolerable, and complex pain condition caused by the primary bone tumor or bone metastasis. CIBP is a combination of complex pain states such as persistent dull pain, spontaneous pain, and mechanical allodynia. Its unique breakthrough pain makes patients suffer because of its unstable onset time and extremely strong pain. The mechanisms of CIBP involves inflammatory, neuropathic factors and specific peripheral local tumor destruction. Approximately 75% of patients with advanced cancer have experienced CIBP. With the survival time of patients with cancer being prolonged, only half of the CIBP can be well controlled. To develop more effective drugs and improve the quality of life of patients with CIBP, it is particularly urgent to extensively study the complex mechanisms of the occurrence and development of CIBP as well as to uncover new targets for developing new analgesics. The spinal cord is the primary center of nociceptive signal processing. During CIBP, unique neurobiochemical changes occur in the spinal cord level. Therefore, the study on the spinal cord level mechanisms of CIBP facilitates the development of efficient and accurate treatment of CIBP. During the development of CIBP, the central sensitization caused by the enhanced information transmission of “neuron glial cells” in the spinal cord is closely related to the central nervous inflammation (mainly activated by glial cells such as astrocytes and microglia). CIBP belongs to the category of “arthralgia” or other diseases in traditional Chinese medicine (TCM). The pathogenesis is mostly the empirical evidence of “impassability leads to pain” and the deficiency syndrome of “dishonor leads to pain”, which is often mixed with deficiency and reality. Treatment should be based on the basic principles of “supporting righteousness and eliminating evil” and “treating both the symptoms and the root cause”. TCM has a good analgesic effect in the treatment of CIBP, of based on syndrome differentiation and treatment tonic agents, rational blood agents, Qi-regulating agents, are mostly used in the selected of prescriptions, with effects as dispelling wind dampness, promoting blood circulation, and removing blood stasis, tonifying deficiency drugs and so on. With the development of integrated traditional Chinese and Western medicine research, the specific mechanisms of TCM to alleviate CIBP is gradually clear. This review summarizes the basic research on the spinal cord mechanism of CIBP and internal treatment of CIBP with TCM in recent 10 years.

Millettia speciosa Champ. is a famous medicinal and edible herb in southeast China. The major constituents of M. speciosa includes flavonoids, alkaloids and so on, which display effects of protecting liver and resisting fatigue. With access to relevant literature, the result shows that the chemical constituents of root and aerial parts in M. speciosa have been studied clearly, while the pharmacological research of M. speciosa is still very preliminary, and there is little application of active constituents for deep pharmacological research and development. Therefore, this paper summarizes the research on the chemical constituents and pharmacological effects of M. speciosa in recent years in order to provide reference for the further development and utilization of M. speciosa active constituents.

Objective

This study investigated effects and underlying mechanisms of Qingda granules (QDG) on cardiac inflammation in spontaneously hypertensive rats (SHRs).

Methods

Twelve SHRs (17 weeks old) were randomly divided into SHR and SHR + QDG groups, with six rats in each group. We also used six 17-week-old Wistar Kyoto (WKY) rats as the WKY group. While rats in the SHR + QDG group were administered QDG (0.8 g/kg/d) for eight weeks, those in the WKY and SHR groups were administered an equal volume of normal saline. Blood pressure was then monitored weekly. Subsequently, hematoxylin and eosin (HE) staining was used to detect pathological changes in the cardiac tissue. Besides, enzyme-linked immunosorbent assay (ELISA) was used to detect the serum content of inflammatory cytokines. Subsequently, real-time quantitative polymerase chain reaction and immunohistochemical (IHC) staining were conducted to determine the expression of inflammatory cytokines and inflammatory cell infiltration, including the activation of the MCP-1/CCR2 signaling pathway.

Results

As observed, QDG inhibited the elevation of systolic blood pressure, diastolic blood pressure, and mean arterial pressure in the understudied SHRs. HE staining showed that this drug attenuated pathological changes and inflammatory cell infiltration of cardiac tissue samples in the SHRs. However, ELISA and IHC confirmed a reduction in the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum and cardiac tissue of SHRs with QDG treatment. Additionally, QDG treatment significantly attenuated protein levels of interferon-γ, CD3, and Mac-2 in the cardiac tissue samples of SHRs. Moreover, mRNA and protein expressions of monocyte chemoattractant protein 1 (MCP-1) and chemotactic cytokine receptor 2 (CCR2), which were upregulated in cardiac tissue samples of SHRs, became downregulated through treatment with QDG.

Conclusion

Therefore, by decreasing the levels of inflammatory cytokines and inflammatory cell infiltration through suppression of the MCP-1/CCR2 signaling pathway, QDG treatment attenuated blood pressure and cardiac inflammatory changes in SHRs.

Somatic reprogramming is a big breakthrough in stem cell technology. A deep understanding of the mechanisms of reprogramming will promote manipulating the cell fates and is expected to treat various diseases caused by the degeneration of functional cells, tissues, and organs. However, the existing reprogramming problems include low efficiency and unsafe, and many small molecules have been found to improve this state. Here in this review, the important roles of natural compounds in reprogramming are summarized, providing new insights into the cell fate transformation.

Objective

To synthesize copper (II) porphyrin complexes and study their interactions with c-myc G-quadruplex DNA.

Methods

The 5-p-hydroxyphenyl-10, 15, 20-tris (p-methoxyphenyl) copper (II) porphyrin complex [p-HTMOPPCu (II)] was synthesized by the conventional heating method. Ultraviolet (UV) titration, fluorescence titration, fluorescence resonance energy transfer (FRET) melting point and competitive assays were used to study the interactions between p-HTMOPPCu (II) and c-myc G-quadruplex DNA.

Results

The UV absorption spectrum and fluorescence spectroscopy results indicated that the complex of p-HTMOPPCu (II) bound better with c-myc G-quadruplex DNA; the FRET melting point assay, and competitive melting point assay demonstrated that p-HTMOPPCu (II) could selectively bind and stabilize c-myc G-quadruplex DNA.

Conclusion

p-HTMOPPCu (II) can bind and stabilize c-myc G-quadruplex DNA and will potentially be developed into a class of small molecule inhibitors targeting c-myc G-quadruplex DNA for clinical applications in the treatment of tumors.

Piericidins are a family of α-pyridone antibiotics with fascinating biological activity produced by actinomycetes, derived from land soil, insect or marine samples. There are 39 natural piericidins reported before 2016, and most of them are obtained from soil actinomycetes. However, marine-derived Streptomyces isolates have been showed great importance to produce piericidins with new structures in recent 5 years. This review covers the 40 natural piericidins reported after 2016, together with their obvious cytotoxic activities against cancer cell lines. Their structure–activity relationships are also discussed briefly. The anti-tumor potential, especially as lead compounds for anti-renal cell carcinoma agents, is of great concern recently. This review helps to provide comprehensive chemical information and new insights into the antitumor potential of piericidins.