Comprehensive effects of traditional Chinese medicine treatment on heart failure and changes in B-type natriuretic peptide levels: A meta-analysis.

BACKGROUND: Heart failure (HF), a common cardiovascular condition, is characterized by significant morbidity and mortality. While traditional Chinese medicine (TCM) is often used as a complementary approach in HF management, systematic evaluations of its impact on clinical outcomes, TCM syndrome scores, and B-type natriuretic peptide (BNP) levels are lacking. This study fills this gap through a comprehensive analysis of randomized controlled trials (RCTs) focusing on TCM for HF treatment. It encompasses an assessment of methodological quality, a meta-analysis, and an evaluation of evidence quality based on established standards. The results offer crucial insights into the potential advantages and constraints of TCM in HF management. AIM: To systematically analyze the effects of TCM on the clinical comprehensive outcomes, TCM syndrome scores, and BNP levels in patients with HF and evaluated the quality of evidence for these trials. METHODS: RCTs on TCM for HF treatment published since the establishment of the database were searched in four Chinese and English databases, including China National Knowledge Infrastructure, Wanfang, VIP Information Chinese Science and Technology Journal, and PubMed. Methodological quality was assessed for the included studies with the Cochrane risk-of-bias assessment tool, and the meta-analysis and publication bias assessment was performed with the RevMan5.3 software. Finally, the quality of evidence was rated according to the GRADE criteria. RESULTS: A total of 1098 RCTs were initially retrieved. After screening, 16 RCTs were finally included in our study, which were published between 2020 and 2023. These RCTs involved 1660 HF patients, including 832 in the TCM group [TCM combined with conventional Western medicine (CMW) treatment] and 828 in the CWM group (CWM treatment). The course of treatments varied from 1 wk to 3 months. TCM syndrome differentiation was analyzed in 11 of the included RCTs. In all included RCTs, outcome indicators included comprehensive clinical outcomes, TCM syndrome scores, and BNP levels. The meta-analysis results showed significant differences between the TCM and CWM groups in terms of comprehensive clinical outcomes [risk ratio = -0.54; 95% confidence interval (CI) = -0.61, -0.47; P < 0.00001], TCM syndrome scores [weighted mean difference (WMD) = -142.07; 95%CI = -147.56, -136.57; P < 0.00001], and BNP levels (WMD = -142.07; 95%CI = -147.56, -136.57; P < 0.00001). According to the GRADE criteria, RCTs where "TCM improves clinical comprehensive outcomes" were rated as low-quality evidence, and RCTs where "TCM reduces TCM syndrome scores" or "TCM decreases BNP levels" were rated as medium-quality evidence. CONCLUSION: TCM combined with CWM treatment effectively improves comprehensive clinical outcomes and diminishes TCM syndrome scores and BNP levels in HF patients. Given the low and medium quality of the included RCTs, the application of these results should be cautious.

Ginsenosides: changing the basic hallmarks of cancer cells to achieve the purpose of treating breast cancer.

In 2021, breast cancer accounted for a substantial proportion of cancer cases and represented the second leading cause of cancer deaths among women worldwide. Although tumor cells originate from normal cells in the human body, they possess distinct biological characteristics resulting from changes in gene structure and function of cancer cells in contrast with normal cells. These distinguishing features, known as hallmarks of cancer cells, differ from those of normal cells. The hallmarks primarily include high metabolic activity, mitochondrial dysfunction, and resistance to cell death. Current evidence suggests that the fundamental hallmarks of tumor cells affect the tissue structure, function, and metabolism of tumor cells and their internal and external environment. Therefore, these fundamental hallmarks of tumor cells enable tumor cells to proliferate, invade and avoid apoptosis. Modifying these hallmarks of tumor cells represents a new and potentially promising approach to tumor treatment. The key to breast cancer treatment lies in identifying the optimal therapeutic agent with minimal toxicity to normal cells, considering the specific types of tumor cells in patients. Some herbal medicines contain active ingredients which can precisely achieve this purpose. In this review, we introduce Ginsenoside's mechanism and research significance in achieving the therapeutic effect of breast cancer by changing the functional hallmarks of tumor cells, providing a new perspective for the potential application of Ginsenoside as a therapeutic drug for breast cancer.

[Inhibitory effects of transfection of arresten gene on liver metastasis from colorectal cancer in nude mice].

BACKGROUND & OBJECTIVE: Liver metastasis is the most common cause of death due to colorectal cancer. Above 50% colorecal cancer patients have liver metastasis. This study was to investigate the effect of transfection of arresten gene on liver metastasis from human colorectal cancer (LoVo) xenografts in nude mice. METHODS: The eukaryotic expression plasmid pSecTag2-arresten was transfected into human colorectal cancer cell line LoVo using Lipofectamine 2000. Cells were divided into pSecTag2-arresten group, pSecTag2 group and control group. Expressions of arresten at mRNA and protein levels were detected by RT-PCR and Western blot, respectively. The effect of arresten on proliferation of LoVo cells was measured using MTT assay. LoVo cells transfected with pSecTag2-arresten were implanted into nude mice to investigate the effect of arresten on hepatic metastasis of colorectal cancer. Microvessel density (MVD) of xenograft tumors was assessed using immunohistochemistry with FVIIIRag monoclonal antibody. RESULTS: Arresten was successfully transfected and expressed in LoVo cells. Inhibition of cell proliferation did not differ significantly in all three groups (P > 0.05). The metastastic rate was lower in pSecTag2-arresten group [(25.1+/-2.1)%] than in pSecTag2 group [(87.1+/-1.2)% or control group [(87.1+/-1.5)%] in LoVo cells (P < 0.05). The number of xenograft tumors and MVD were higher in pSecTag2-arresten group [(4.5 +/-0.5) and (15.3+/-3.5)] than in pSecTag2 group [(19.6+/-2.5) and (42.2+/-2.6)] or in control group [(20.4+/-2.5)and (45.6+/-5.1)] in nude mice. CONCLUSION: Arresten can inhibit hepatic metastasis from colorectal cancer, which may be through its inhibition on tumor angiogenesis.

[Herpes simplex virus-thymidine kinase gene transduced into T cell clone in the treatment of ulcerative colitis in rat].

OBJECTIVE: To investigate the effect of herpes simplex virus-thymidine kinase (HSV-TK) gene transduced into T cell clone on the treatment of ulcerative colitis (UC) in rat. METHODS: The T cell clone transduced with HSV-tk was infused into 27 rats with UC. Changes of stimulation index (SI), CD4(+), CD8(+), IL-13, IL-4 were detected, and pathological changes before and after infusion was compared. RESULTS: In the second and third day after tk+ T clone infusion, the inflammation of colon was assimilated. Two weeks later, the colon began to renovate and mend. The average SI was 7.39+/-1.24 before infusion, and 2.67+/-0.87 after infusion (P<0.05). Peripheral blood levels of CD4(+), CD8(+) or IL-13 and IL-4 in therapeutic group were significantly decreased as compared to control group (P<0.05). CONCLUSION: HSV-tk gene transduced into T lymphocyte clone and infused back is effective for UC gene therapy and target design in rat.

Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration.

AIM: To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS: Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS: SMYD3 over-expression in HCC was associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de-methylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% +/- 7.97%, Pgenesil-1-s2 72.14% +/- 9.68% vs Pgenesil-1-hk 6.89% +/- 4.12%, P < 0.01) and migration (Pgenesil-1-s1 4.24% +/- 1.58%, Pgenesil-1-s1 4.87% +/- 0.73% vs Pgenesil-1 19.03% +/- 4.63%, Pgenesil-1-hk 19.95% +/- 5.21%, P < 0.01) and induced apoptosis (FCM subG1 phase Pgenesil-1-s1 19.07% +/- 1.78%, Pgenesil-1-s2 17.68% +/- 2.36% vs Pgenesil-1 0.47% +/- 0.12%, Pgenesil-1-hk 1.46% +/- 0.28%, P < 0.01. TUNEL-positive cells: Pgenesil-1-s1 40.24% +/- 5.18%, Pgenesil-1-s2 38.48% +/- 4.65% vs Pgenesil-1 2.18% +/- 1.34%, Pgenesil-1-hk 2.84% +/- 1.22%, P < 0.01) in HepG2 cells. CONCLUSION: These results demonstrate that SMYD3 plays a critical role in the carcinogenesis and progression of HCC. The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZ1 CpG promoter hypermethylation.

[Experimental research of therapeutic effect on hepatocellular carcinoma of targeting SMYD3 gene inhibition by RNA interference].

OBJECTIVE: To determine the potential of SMYD3 as a therapeutic target for hepatocellular carcinoma (HCC) by potent and highly sequence-specific RNA interference (RNAi) technique. METHODS: The mRNA of SMYD3 was detected by RT-PCR in different HCC cell lines, such as HepG2, Hep3B and SMMC7721. Recombinant SMYD3 shRNA plasmid Pgenesil-1-s was constructed and transfected into HepG2 cells, and Western blot was used to identify the down regulation of SMYD3 protein expression after transfection. MTT and flow cytometry analysis (FCM) were respectively applied to analysis cell proliferation and apoptosis. In vivo study was carried out by injecting recombinant SMYD3 shRNA plasmids into transplanted tumors of nude mice. RESULTS: The expression of SMYD3 mRNA was abundant in HCC cell lines HepG2, Hep3B, SMMC7721, whereas none in normal hepatic cell line L-02. RNA interference was able to suppress SMYD3 expression greatly and then inhibited cell growth effectively and induced apoptosis of HepG2 cells efficiently. After injection of recombinant SMYD3 shRNA plasmid, transplanted tumors grew slowly and reduced in size and weight when compared with those of control groups (P < 0.01). CONCLUSIONS: SMYD3 plays a major role in occurrence and progress of HCC. Inhibition of SMYD3 by RNAi can induce apoptosis in HepG2 cells and suppress tumor growth in nude mice. Therefore SMYD3 could be an ideal therapeutic target for HCC.

[Inhibition of SMYD3 gene expression by RNA interference induces apoptosis in human hepatocellular carcinoma cell line HepG2].

BACKGROUND & OBJECTIVE: SET and MYND domain-containing protein 3 (SMYD3) gene was found to encode a histone methyltransferase involved in the proliferation and apoptosis of cancer cells. This study was to detect the expression of SMYD3 in hepatocellular carcinoma (HCC) cell lines, and reveal its function of regulating proliferation and apoptosis of HCC cell line through gene silencing. METHODS: The expression of SMYD3 in HCC cell lines HepG2, Hep3B, SMMC7721, and normal hepatic cell line L-02 was detected by reverse transcription-polymerase chain reaction (RT-PCR); its expression in 24 specimens of HCC and peri-cancer tissue was detected by immunohistochemistry. Short hairpin RNA (shRNA) plasmids Pgenesil-1-s1 and Pgenesil-1-s2 (with interfering effect), and Pgenesil-1-hk (without interfering effect) were constructed and transfected into HepG2 cells. Western blot was used to detect the expression of SMYD3 protein after transfection. Cell proliferation was analyzed by MTT assay; cell apoptosis was analyzed by flow cytometry (FCM) and TUNEL. RESULTS: SMYD3 was overexpressed in the HCC cell lines and HCC tissue. After transfection with shRNA, SMYD3 expression in HepG2 cells was down-regulated by 75%-85%, and the cell growth was inhibited by 60.95%-72.14%. The apoptosis rate of HepG2 cells was significantly higher in Pgenesil-1-s1 and Pgenesil-1-s2 groups than in Pgenesil-1-hk and Pgenesil-1 groups [(17.68+/-2.36)% and (19.07+/-1.78)%, vs. (1.44+/-0.28)% and (0.47+/-0.12)%, P<0.01]. CONCLUSION: SMYD3 is overexpressed in various HCC cell lines and HCC tissue; RNA interference can down-regulate SMYD3 expression, inhibit proliferation and promote apoptosis of HepG2 cells.

[Suppression of SMYD3 expression in HepG2 cell by shRNA interference].

OBJECTIVES: To identify the inhibition effect of shRNA on the SMYD3 (SET- and MYND-domain containing protein-3) expression in hepatoma cell line HepG2 through gene silencing. METHODS: Two reverse repeated motifs targeting on the SMYD3 mRNA sequences 267-288, 302-323 respectively, were synthesized and inserted into the mock plasmid pGenesil-1 which expressed EGFP to create recombinant plasmids pGenesil-1-s1 and pGenesil-1-s2. pGenesil-1-hk specific to no SMYD3 mRNA sequence served as a control. After transfection into HepG2 cells, RT-PCR and western blot were applied to identify the down regulation of SMYD3 expression by shRNAs. RESULTS: All plasmids were constructed successfully. pGenesil-1-s1, pGenesil-1-s2 inhibited the mRNA and protein expression of SMYD3 in HepG2 cells. There was a significant distinction when compared with pGenesil-1-hk and pGenesil-1 (P<0.01). CONCLUSION: Short hairpin RNAs can efficiently and specifically suppress the expression of SMYD3 in HepG2 cells.

[Expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension].

OBJECTIVE: To investigate the expression of local angiotensinogen mRNA and activation of local nuclear factor-kappaB in vasculopathy of portal hypertension and to discuss their role in the pathogenesis of portal hypertensive vasculopathy. METHODS: RT-PCR was used to detect the expression of local angiotensinogen mRNA in 28 specimens of splenic artery and vein obtained during operation of elective separation and amputation on 28 portal hypertension (PH) patients, 20 males and 8 females, aged 51.7 +/- 10 (30 - 65), and in 12 specimens of normal vessel from 12 patients undergoing splenectomy due to traumatic rupture of spleen. Chemiluminescent electrophoretic mobility shift assay (EMSA) was used to detect the activation of NF-kappaB in splenic artery and vein. RESULTS: The levels of local angiotensinogen mRNA in the splenic artery and vein of PH group were 0.48 +/- 0.21 and 0.43 +/- 0.16 respectively, both significantly higher than those in the control group (0.23 +/- 0.12 and 0.18 +/- 0.10, both P < 0.05). There was no significant difference between the splenic artery and vein in the expression of local angiotensinogen mRNA in PH group. The activation levels of NF-kappaB in splenic artery and vein of the PH patients were 1.44 +/- 0.23 and 1.38 +/- 0.18 respectively, both significantly higher than those of the control group (0.19 +/- 0.20 and 0.25 +/- 0.16 respectively, both P < 0.05). However, there was no significant difference in the activation levels of NF-kappaB between the splenic artery and vein in the PH patients (P > 0.05). CONCLUSION: Local angiotensinogen and activation of NF-kappaB maybe one of the factors in the pathogenesis of portal hypertensive vasculopathy, which can cause and advance portal hypertensive vasculopathy.