Exploring the effects and mechanisms of Guizhigancao Decoction on heart failure using an integrated approach based on experimental support and network pharmacology strategy.

Background and aim: HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed. Experimental procedure: In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF in vivo. An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF. Results and conclusions: The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

Brown adipose tissue activation with ginsenoside compound K ameliorates polycystic ovary syndrome.

BACKGROUND AND PURPOSE: Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disease affecting women of reproductive age. Due to its complex aetiology, there is no currently effective cure for PCOS. Brown adipose tissue (BAT) activity is significantly decreased in PCOS patients, and BAT activation has beneficial effects in animal models of PCOS. Here, we investigated the effect of ginsenoside compound K (CK) in an animal model of PCOS and its mechanism of BAT activation. EXPERIMENTAL APPROACH: Primary brown adipocytes, Db/Db mice and dehydroepiandrosterone (DHEA)-induced PCOS rats were used. The core body temperature, oxygen consumption, energy metabolism related gene and protein expression were assessed to identify the effect of CK on overall energy metabolism. Oestrous cycle, serum sex hormone, ovarian steroidogenic enzyme gene expression and ovarian morphology were also evaluated following CK treatment. KEY RESULTS: Our results indicated that CK treatment could significantly protect against body weight gain in Db/Db mice via BAT activation. Furthermore, we found that CK treatment could normalize hyperandrogenism, oestrous cyclicity, normalize steroidogenic enzyme expression and decrease the number of cystic follicles in PCOS rats. Interestingly, as a potential endocrine intermediate, C-X-C motif chemokine ligand-14 protein (CXCL14) was significantly up-regulated following CK administration. In addition, exogenous CXC14 supplementation was found to reverse DHEA-induced PCOS in a phenotypically similar manner to CK treatment. CONCLUSION AND IMPLICATIONS: In summary, CK treatment significantly activates BAT, increases CXCL14 expression and ameliorates PCOS. These findings suggest that CK might be a potential drug candidate for PCOS treatment.

Traditional Chinese Medicine Enema Therapy in a Patient With a Confirmed Negative SARS-CoV-2 Test in the Respiratory Tract but Positive in the Intestinal Tract: A Case Report.

We report the case of a 43-year-old man who was infected with SARS-CoV-2 in February 2020 and actively cooperated with treatment in the hospital. During the course of treatment, we found that the respiratory SARS-CoV-2 nucleic acid became negative, but remained positive in the intestinal tract. As a result, we adjusted the treatment plan to include traditional Chinese medicine enema treatment. The patient had negative intestinal SARS-CoV-2 nucleic acid test within 4 days, and the subsequent repeated review of intestinal SARS-CoV-2 nucleic acid was negative, and the virus was undetectable. It is suggested that traditional Chinese medicine enema treatment may be helpful to remove the SARS-CoV-2 in the intestines of patients with COVID-19 infection, and may support the treatment of patients with respiratory SARS-CoV-2 nucleic acid negative and positive in the intestinal tract.

Photoactivation of Akt1/GSK3ß Isoform-Specific Signaling Axis Promotes Pancreatic ß-Cell Regeneration.

Promotion of insulin-secreting ß-cell regeneration in patients with diabetes is a promising approach for diabetes therapy, which can contribute to rescue the uncontrolled hyperglycemia. Low-power laser irradiation (LPLI) has been demonstrated to regulate multiple physiological processes both in vitro and in vivo through activation of various signaling pathways. In the present study, we showed that LPLI promoted ß-cell replication and cell cycle progression through activation of Akt1/GSK3ß isoform-specific signaling axis. Inhibition of PI3-K/Akt or GSK3 with specific inhibitors dramatically reduced or increased LPLI-induced ß-cell replication, revealing Akt/GSK3 signaling axis was involved in ß-cell replication and survival upon LPLI treatment. Furthermore, the results of shRNA-mediated knock down of Akt/GSK3 isoforms revealed that Akt1/GSK3ß isoform-specific signaling axis regulated ß-cell replication and survival in response to LPLI, but not Akt2/GSK3α. The mechanism by which LPLI promoted ß-cell replication through Akt1/GSK3ß signaling axis involved activation of ß-catenin and down-regulation of p21. Taken together, these observations suggest that Akt1/GSK3ß isoform signaling axis play a key role in ß-cell replication and survival induced by LPLI. Moreover, our findings suggest that activation of Akt1/GSK3ß isoform signaling axis by LPLI may provide guidance in practical applications for ß-cell regenerative therapies.

[Effect of puerarin preconditioning on cytokine levels in patients undergoing cardiopulmonary bypass in perioperative period].

OBJECTIVE: To study the effect and acting mechanism of puerarin preconditioning (PP) on blood level of cytokines in patients undergoing cardiopulmonary bypass (CPB) in perioperative period. METHODS: Forty patients with heart diseases scheduled to take surgical operation were randomized into the control group and the PP group equally. They were treated with the same program, excepting that 0.6 g of puerarin was given to the PP group by adding in 5% glucose solution 250 mL for intravenous dripping every day for one week before operation, but to the control group, normal saline was given instead. The levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6, 8 and 10 (IL-6, IL-8, IL-10) in arterial blood were measured at 5 time points in the process of CPB, namely, anesthetic induction (T1), 10 min after the clamp of the ascending aorta (T2), 10 min, 2 h and 12 h after the Clamped aorta is unclamped (T3, T4 and T5). RESULTS: All the above-mentioned indexes (TNF-alpha, IL-6, IL-8 and IL-10) gradually increased after beginning CPB, reached the peak at T4, then lowered gradually but still presented the higher levels at T5 than those at T1 (P < 0.05). Comparison between the two groups showed that levels of TNF-alpha, IL-6 and IL-8 were significantly lower (P < 0.05 or P < 0.01) and level of IL-10 was higher in the PP group than those in the control group respectively at all the time points (P < 0.01). CONCLUSION: Injecting puerarin before CPB could effectively suppress the pro-inflammatory cytokines like TNF-alpha, IL-6 and IL-8; and enhance the expression of anti-inflammatory cytokines like IL-10, thus to alleviate the inflammatory reaction induced by CPB.