A peripheral system disease-Pulmonary hypertension.

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It is a chronic condition characterized by intricate pathogenesis and uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification on PH. PH is not only a pulmonary vascular disease, but also a systemic disease. The findings emphasize that the onset of PH is not exclusively confined to the pulmonary vasculature, consequently necessitating treatment approaches that extend beyond targeting pulmonary blood vessels. Hence, the research on the pathological mechanism of PH is not limited to target organs such as pulmonary vessels, but also focuses on exploring other fields (such as estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, and histone modification).

Acupuncture modification treatment for female sexual dysfunction: A meta-analysis.

BACKGROUND: Acupuncture has potential in the treatment of female sexual dysfunction (FSD), but its effectiveness needs to be verified. AIM: A meta-analysis to provide a summary of studies that had investigated the efficacy of acupuncture as a treatment for FSD. METHODS: A systematic screening was conducted on electronic databases such as Pubmed, Embase, Cochrane Library, CNKI, and CBM to select studies that met the criteria before April 2023. We only included those studies assessing women's sexual functioning by the Female Sexual Function Index (FSFI). OUTCOMES: By calculating the relative risk (RR) using the standardized mean difference (SMD) and 95% confidence interval (CI), these data were combined to generate a summary of the findings. The pooled results were calculated using a random-effects model. RESULTS: A total of 4 studies involving 178 participants were included, and the comprehensive results indicated a significant difference in FSFI scores between the acupuncture group and the control group. In the desire and arousal scale, there was a statistically significant difference between the acupuncture group and the control group. But in the scale of lubrication, orgasm, satisfaction, and pain, there was no statistically significant difference between the two groups. CONCLUSION: A comparison of overall FSFI scores, sexual desire, and sexual arousal revealed that acupuncture treatment can improve female sexual dysfunction to some extent. However, in terms of vaginal lubrication, orgasm, sexual satisfaction, and sexual pain, acupuncture treatment did not significantly improve female sexual dysfunction. In the future, it is necessary to include more RCT trials and expand the number of patients analyzed to make the conclusions more reliable.

Development of Glycyrrhetinic Acid and Folate Modified Cantharidin Loaded Solid Lipid Nanoparticles for Targeting Hepatocellular Carcinoma.

Cantharidin (CTD) is the major component of anticancer drugs obtained from Mylabris Cichorii and has a good inhibitory effect on several cancers, including hepatocellular carcinoma (HCC) and breast cancer. However, due to its toxicity, oral administration can cause various adverse reactions, limiting its clinical application. The aim of this work was to design glycyrrhetinic acid (GA)- and/or folate (FA)-modified solid lipid nanoparticles (SLNs) for the encapsulation of CTD to target HCC. Four CTD-loaded SLNs (cantharidin solid lipid nanoparticles (CSLNs), glycyrrhetinic acid-modified cantharidin solid lipid nanoparticles (GA-CSLNs), folate-modified cantharidin solid lipid nanoparticles (FA-CSLNs), and glycyrrhetinic acid and folate-modified cantharidin solid lipid nanoparticles (GA-FA-CSLNs)) were prepared by the emulsion ultrasonic dispersion method, and their physicochemical parameters were determined (particle size and distribution, morphology, zeta-potential, entrapment efficiency, drug loading, and hemolysis). Additionally, the antitumor activities of the four SLNs were evaluated comprehensively by tests for cytotoxicity, cell migration, cell cycle, apoptosis, cellular uptake, competition suppression assay, and in vivo tumor suppression assay. Four SLNs showed spherical shapes and mean diameters in the range of 75-110 nm with size dispersion (PDI) within the range of 0.19-0.50 and zeta-potential approximately -10 mV. The entrapment efficiency of CTD in SLNs was higher than 95% for all tested formulations, and no hemolysis was observed. Compared to GA-CSLNs or CSLNs, GA-FA-CSLNs and FA-CSLNs showed stronger cytotoxicity on hepatocellular carcinoma cells (HepG2), and the cytotoxicity of GA-FA-CSLNs on hepatocyte cells (L-02) was remarkably reduced compared with other formulations. GA-FA-CSLNs and FA-CSLNs also increased the inhibition of HepG2 cell migration, and FA-CSLNs had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells were arrested mainly in the S phase and G2/M phase. Analysis of competition inhibition experiments showed that GA and FA ligands had targeted effects on HepG2 cells. The in vivo tumor inhibition experiment showed that GA-FA-CSLNs and FA-CSLNs had excellent tumor inhibition ability-their tumor inhibition rates were 96.46% and 89.92%, respectively. Our results indicate that GA-FA-CSLNs and FA-CSLNs have a promising future in the therapeutic intervention of HCC.

18-GA-Suc Modified Liposome Loading Cantharidin for Augmenting Hepatic Specificity: Preparation, Characterization, Antitumor Effects, and Liver-Targeting Efficiency.

Cantharidin (CTD), a natural Chinese medicine constituent extracted from mylabris, is a potent drug against hepatocellular carcinoma. However, the clinical application of CTD was limited because of its toxicity and low solubility. In this work, a novel CTD-loaded liposome modified with 3-succinyl-30-stearyl glycyrrhetinic acid (18-GA-Suc-CTD-Lip) was prepared to enhance liver-targeting efficiency and antitumor activity. 18-GA-Suc-CTD-Lip and CTD-Lip were successfully prepared by film dispersion method and totally characterized. The antitumor effects in vitro were evaluated by cell proliferation inhibition assay, transwell assay, cell cycle analysis, and an apoptosis test. Pharmacokinetic and biodistribution were all investigated to precisely reveal liver-targeting efficiency of 18-GA-Suc-CTD-Lip in vivo. The IC50 values of 18-GA-Suc-CTD-Lip in HepG2 (3.417 ± 0.165 nmol/L) and Huh-7 (4.478 ± 0.409 nmol/L) cells were much lower than that of CTD-Lip, indicating that antitumor effects of 18-GA-Suc-CTD-Lip were remarkable because of the modification of 18-GA-Suc. The maximum concentration in the liver of 18-GA-Suc-CTD-Lip (1.72 ± 0.14 µg/g) was more than twice CTD-Lip (0.75 ± 0.08 µg/g) at 30 min, illustrating that 18-GA-Suc-CTD-Lip possesses excellent liver-targeting efficiency. Conclusively, 18-GA-Suc-CTD-Lip could be a potential liver-targeting antitumor drug for hepatocellular carcinoma.

Development of 11-DGA-3-O-Gal-Modified Cantharidin Liposomes for Treatment of Hepatocellular Carcinoma.

BACKGROUND: Liver cancer is a common malignant tumor worldwide, and its morbidity and mortality increase each year. The disease has a short course and high mortality, making it a serious threat to human health. PURPOSE: The objective of this study was to create novel liver-targeting nanoliposomes to encapsulate cantharidin (CTD) as a potential treatment for hepatic carcinoma. METHODS: 3-Galactosidase-30-stearyl deoxyglycyrrhetinic acid (11-DGA-3-O-Gal)-modified liposomes (11-DGA-3-O-Gal-CTD-lip) for the liver-targeted delivery of CTD were prepared via the film-dispersion method and characterized. In vitro analyses of the effects on cellular cytotoxicity, cell migration, cell cycle, and cell apoptosis were carried out and an in vivo pharmacokinetics study and tissue distribution analysis were performed. RESULTS: Compared with unmodified liposomes (CTD-lip), 11-DGA-3-O-Gal-CTD-lip showed higher cytotoxicity and increased the inhibition of HepG2 cell migration, but they did not increase the apoptotic rate of cells. The inhibition mechanism of 11-DGA-3-O-Gal-CTD-lip on hepatocellular carcinoma was partly through cell cycle arrest at the S phase. Analysis of pharmacokinetic parameters indicated that 11-DGA-3-O-Gal-CTD-lip were eliminated more rapidly than CTD-lip. Regarding tissue distribution, the targeting efficiency of 11-DGA-3-O-Gal-CTD-lip to the liver was (41.15 ± 3.28)%, relative targeting efficiency was (1.53 ± 0.31)%, relative uptake rate was( 1.69 ± 0.37)%, and peak concentration ratio was (2.68 ± 0.12)%. CONCLUSION: 11-DGA-3-O-Gal-CTD-lip represent a promising nanocarrier for the liver-targeted delivery of antitumor drugs to treat hepatocellular carcinoma.