The role of competing endogenous RNA network in the development of hepatocellular carcinoma: potential therapeutic targets.

The current situation of hepatocellular carcinoma (HCC) management is challenging due to its high incidence, mortality, recurrence and metastasis. Recent advances in gene genetic and expression regulation have unveiled the significant role of non-coding RNA (ncRNA) in various cancers. This led to the formulation of the competing endogenous RNA (ceRNA) hypothesis, which posits that both coding RNA and ncRNA, containing miRNA response elements (MRE), can share the same miRNA sequence. This results in a competitive network between ncRNAs, such as lncRNA and mRNA, allowing them to regulate each other. Extensive research has highlighted the crucial role of the ceRNA network in HCC development, impacting various cellular processes including proliferation, metastasis, cell death, angiogenesis, tumor microenvironment, organismal immunity, and chemotherapy resistance. Additionally, the ceRNA network, mediated by lncRNA or circRNA, offers potential in early diagnosis and prevention of HCC. Consequently, ceRNAs are emerging as therapeutic targets for HCC. The complexity of these gene networks aligns with the multi-target approach of traditional Chinese medicine (TCM), presenting a novel perspective for TCM in combating HCC. Research is beginning to show that TCM compounds and prescriptions can affect HCC progression through the ceRNA network, inhibiting proliferation and metastasis, and inducing apoptosis. Currently, the lncRNAs TUG1, NEAT1, and CCAT1, along with their associated ceRNA networks, are among the most promising ncRNAs for HCC research. However, this field is still in its infancy, necessitating advanced technology and extensive basic research to fully understand the ceRNA network mechanisms of TCM in HCC treatment.

Qijia rougan formula ameliorates ECM deposition in hepatic fibrosis by regulating the JAK1/STAT6-microRNA-23a feedback loop in macrophage M2 polarization.

Hepatic fibrosis is the critical pathological stage in the progression of chronic liver disease to cirrhosis and hepatocellular carcinoma (HCC). However, no approved anti-hepatic fibrosis drugs are available currently. Qijia Rougan Formula (QRF) is a traditional Chinese medicine (TCM) with significant clinical efficacy on hepatic fibrosis. It was derived from Sanjiasan, a famous decoction documented in the Book of Treatise on the Pestilence in the Ming Dynasty of China. However, the underlying regulatory mechanisms remain elusive. This study further confirmed the therapeutic effects of QRF on hepatic fibrosis and dissected its underlying molecular mechanisms from the perspective of macrophage M2 polarization, one of the critical events in hepatic fibrosis. Experimentally, QRF significantly improved extracellular matrix (ECM) deposition and fibrosis in the liver of model rats. QRF diminished the proportion of M2 macrophages, decreased the levels of TGF-ß, PDGFB and IL-10, and regulated the expression of p-JAK1, p-STAT6, JAK1 and microRNA-23a both in vitro and in vivo. Collectively, it was confirmed that QRF effectively improves liver function and hepatocyte damage, and reduces ECM deposition. QRF ameliorates hepatic fibrosis by regulating JAK1/STAT6-microRNA-23a negative feedback loop to inhibit macrophage M2 polarization and thus reduce ECM deposition. Our study illustrates the potential of QRF for hepatic fibrosis therapy, suggesting that QRF is a promising anti-hepatic fibrosis drug candidate.

Epidemiological investigation and proteomic profiling of typical TCM syndrome in HIV/AIDS immunological nonresponders.

HIV/AIDS pandemic remains the world's most severe public health challenge, especially for HIV/AIDS immunological nonresponders (HIV/AIDS-INRs), who tend to have higher mortality. Due to the advantages in promoting patients' immune reconstitution, Traditional Chinese medicine (TCM) has become one of the mainstays of complementary treatments for HIV/AIDS-INRs. Given that effective TCM treatments largely depend on precise syndrome differentiation, there is an increasing interest in exploring biological evidence for the classification of TCM syndromes in HIV/AIDS-INRs. In our study, to identify the typical HIV/AIDS-INRs syndrome, an epidemiological survey was first conducted in the Liangshan prefecture (China), a high HIV/AIDS prevalence region. The key TCM syndrome, Yang deficiency of spleen and kidney (YDSK), was evaluated by using a tandem mass tag combined with liquid chromatography-tandem mass spectrometry (TMT-LC-MS/MS). A total of 62 differentially expressed proteins (DEPs) of YDSK syndrome compared with healthy people were screened out. Comparative bioinformatics analyses showed that DEPs in YDSK syndrome were mainly associated with response to wounding and acute inflammatory response in the biological process. The pathway annotation is mainly enriched in complement and coagulation cascades. Finally, the YDSK syndrome-specific DEPs such as HP and S100A9 were verified by ELISA, and confirmed as potential biomarkers for YDSK syndrome. Our study may lay the biological and scientific basis for the specificity of TCM syndromes in HIV/AIDs-INRs, and may provide more opportunities for the deep understanding of TCM syndromes and the developing more effective and stable TCM treatment for HIV/AIDS-INRs.

HMGB1/PTEN/PI3K axis participates in the peripheral immune cell differentiation in two representative TCM syndromes of chronic hepatitis B patients.

Liver depression and spleen deficiency syndrome (LDSDS) and spleen-gastric damp-heat syndrome (SGDHS) are two major traditional Chinese medicine syndromes observed in chronic hepatitis B (CHB). Both syndromes exhibit significant differences in the pathogenesis and prognosis, and are closely related to the immune system. However, the underlying mechanisms are largely unknown. This study aimed to explore the immunoregulatory mechanisms of the two syndromes and promote the differentiation precision between the two syndromes. Thirty-six patients with CHB (18 LDSDS patients and 18 SGDHS patients) and 14 healthy controls were recruited into this study and blood was collected from all the subjects for testing. We studied the contents of T lymphocytes by flow cytometry and the expression levels of HMGB1/PTEN/PI3K axis proteins by enzyme-linked immunosorbent assay (Elisa). Protein-protein interaction (PPI) networks among HMGB1/PTEN/PI3K axis were constructed for functional enrichment. The correlations between T lymphocytes and proteins were analyzed by constructing multiple regression equations. The results revealed that the CD8+ T cells level in the two syndromes were lower than that in healthy controls, and the levels of Th17, Treg cells, and HMGB1, PI3K, PDK1, Akt were higher than those of the healthy controls (p < 0.05). Moreover, the levels of CD4+ T, Th17 cells, and HMGB1, PTEN, PI3K in LDSDS were higher than SGDHS (p < 0.05). PPI network indicated that HMGB1/PTEN/PI3K axis participated in T cell activation and liver pathology. Our results revealed that HMGB1/PTEN/PI3K axis may play an important role in regulating the formation of peripheral immune differences between the two syndromes. CD4+ T and Th17 are two representative immune cells that may serve as potential biological markers for LDSDS and SGDHS in CHB.

Sheng-Xue-Xiao-Ban Capsule-induced ischemic colitis and pulmonary embolism in an idiopathic thrombocytopenic purpura patient: a rare case report.

Background: Sheng-Xue-Xiao-Ban Capsule (SXXBC), as a classic Chinese traditional medicine comprised of natural indigo, cortex moutan, forsythia, herba agrimoniae, and licorice, exhibits a heat-clearing and detoxicating function, hemostasis, and stasis dissipation, which is widely applied to treat idiopathic thrombocytopenic purpura (ITP). However, report on ischemic colitis and pulmonary embolism induced by SXXBC therapy is never disclosed. We report the case of an ITP patient who received SXXBC for ascending platelets that then induced ischemic colitis and pulmonary embolism. Case Description: A 74-year-old female patient was admitted in June 2021 due to "bleeding in stool for 1 day," she was then re-admitted in July 2021 due to "repeated bleeding in stool for 2 days". Abdominal computed tomography (CT), colonoscopy, and a pathological examination suggested ischemic colitis according to the American College of Gastroenterology (ACG) clinical guidelines. Pulmonary artery CT angiography suggested pulmonary embolism reflected by multiple filling defects, and the patient presented with shortness of breath. It was noted that the patient had started taken SXXBC for ascending platelets 2 months before the onset of hematochezia. After the diagnosis of hematochezia was made, the patient received phenethylamine and carbazochrome for hemostasis, mesalazine enteric-coated tablets for anti-inflammation, and SXXBC was stopped. The hematochezia then ceased, and the ischemic colitis was attenuated. Afterwards, low-molecular-weight heparin was administered, followed by a 3-week treatment of rivaroxaban anticoagulant, which was taken orally after discharge. The pulmonary embolism was then obviously ameliorated. After excluding other causes, the patient was diagnosed with SXXBC-induced ischemic colitis complicated by pulmonary embolism. After conducting research, we came to the view that natural indigo, which is the main component of SXXBC, contributed to the patient's illness. Conclusions: Ischemic colitis complicated with pulmonary embolism are rare; however, close attention such as regular abdominal CT test needs to be paid and preventive steps such as anti-coagulant treatment could to be taken (if symptoms occur) when treating patients with SXXBC.

Study on the Expression Differences and the Correlation with H2BE Gene of Th Related Cytokines in SSDHS and LDSDS TCM-Syndromes of CHB Patients.

Although our previous studies revealed that H2BE exhibited significantly differential expression between two CHB TCM-syndromes: Spleen-stomach dampness-heat syndrome, SSDHS and liver-depression spleen-deficiency syndrome, LDSDS, the underlying mechanisms remain largely unknown. Recent studies showed that dynamic expression fluctuation of Th related cytokines in CHB TCM-syndromes, and furthermore, their expression levels were largely regulated by H2BE. This study aims to detect the expression level differences of Th related cytokines between these two TCM-syndromes and further investigate the underlying regulatory mechanisms. The expression levels of the four Th related cytokines and H2BE were analyzed and the protein-protein interaction networks between H2BE and the four cytokines were constructed. Our results suggested that almost all the cytokines were significantly upregulated compared with the healthy group (P < 0.05). Interestingly, among the four cytokines, only IL-4 and INF-γ showed statistical significance between these two syndromes. The protein-protein interaction networks demonstrated that H2BE was indirectly associated with IL-4 and IL-10, and H2BE may regulate the expression levels of cytokines through GATA3. Taken together, our results indicated that IL-4 and INF-γ are two representative cytokines that may serve as two potential biochemical indicators of SSDHS and LDSDS in CHB patients; except what has been reported, our study found that one possible way for H2BE to regulate the expression of cytokines is to interact with GATA3 directly or indirectly.

[Comparative analysis of four kinds of vitamin B of milk of lactating mothers and maternal and infant nutritional status in Chinese urban and rural areas].

OBJECTIVE: To understand the nutritional level of lactating mothers and infant by detecting the content of the vitamin B1, vitamin B2, vitamin B6, nicotinic of milk of urban and rural areas and to provide the basis for improving vitamin nutritional status of lactating women and their babies. METHODS: Totally 92 pairs of breastfeeding healthy mothers and their children in Shandong Province were selected. 34 pairs were in a urban area and 58 pairs were in a rural area. Collect the milk of selected lactating mothers and the urine of the lactating mothers and their children. Detect the content of vitamin B1, vitamin B2, vitamin B6, nicotinic of milk of lactating mothers and the content of vitamin B1, vitamin B2, nicotinic of urine of lactating mothers and their children. RESULTS: The content of vitamin B2, vitamin B6 and niacin of milk of urban lactating mothers were significantly higher than that of rural lactating mothers. The results of detection showed the vitamin B2 of milk of urban lactating mothers was 149.77 microg/100 g, which was significantly higher than that of rural women in 85.09 microg/100 g (P < 0.05). Vitamin B6 and niacin contents were 15.29 microg/100 g, 40.83 microg/100 g, which were also higher than that in rural lactating milk (6.69 microg/100 g and 24.48 microg/100 g) (All values P < 0.05). However, vitamin B1 of milk of urban and rural lactating mothers were 5.54 microg/100 g and 4.80 microg/100 g respectively, which had no significant difference. Urine analysis showed vitamin B2 and niacin of urban mothers and children were significantly higher than that in rural area (P < 0.05). But the level of vitamin B1 of rural children was higher than that of urban children (P < 0.05). There was no significant difference in the vitamin B1 between urban and rural mothers. The insufficient percentages of vitamin B1, vitamin B2. niacin in urban mothers was 23.5%, 32.3% and 17.6%, and that in rural mothers were 29.3%, 82.8% and 53.4%. The deficiency percentage of vitamin B1, vitamin B2, niacin in urban children were 2.9%, 2.9% and 11.8%, and that in rural children were 5.1%, 51.8% and 25.8%. CONCLUSION: The insufficient percentage of vitamin B1 in urban and rural mothers was high and the content of vitamin B1 of milk was low. While the insufficient percentage of vitamin B2, niacin of rural lactating mothers and children were higher than that of urban mothers and children.