Therapeutic effects of herbal-medicine combined therapy for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

Background/Aim: Since 2019, the COVID-19 pandemic has been a devastating disease affecting global health to a great extent. Some countries have added on herbal medicines as a complementary treatment for combating COVID-19 due to the urgency of stopping the spread of this viral disease. However, whether these herbal medicines are effective is uncertain. This systematic review and meta-analysis aimed to evaluate the effects of herbal medicine combined therapy in the treatment of COVID-19. Methods: A literature search was performed following the PRISMA Statement and without language restrictions. Seven databases were searched from inception through December 2021. All selected studies were randomized clinical trials (RCTs). Comparing the effects of herbal medicine combined therapy with conventional western medicine, including improvement of clinical symptoms, chest CT images, viral conversion rate, C-reactive protein (CRP) and interleukin 6. Cochrane criteria were applied to examine the methodological quality of the enrolled trials; and meta-analysis software (RevMan 5.4.1) was used for data analysis. Results: In total, the data of 5,417 participants from 40 trials were included in this systematic review; and 28 trials were qualified for meta-analysis. The trials had medium-to-high quality based on GRADE system. Meta-analysis showed that combining herbal medicine vs conventional treatment in 1) coughing (1.43 95% CI:1.21, 1.71, p = 0.0001), 2) fever (1.09 95% CI:1.00, 1.19, p = 0.06), 3) fatigue (1.21 95% CI:1.10, 1.33, p = 0.0001); 4) CT images (1.26 95% CI:1.19, 1.34, P ≤ 0.00001), 5) viral conversion rates (1.22 95% CI:1.06, 1.40, p = 0.005) and 6) viral conversion times (-3.72 95% CI: -6.05, -1.40, p = 0.002), 7) IL6 change (1.97 95% CI: -0.72, 4.66, p = 0.15) and 8) CRP change (-7.92 95% CI: -11.30, -4.53, P ≤ 0.00001). Conclusion: Herbal medicine combined therapy significantly reduces COVID-19 clinical symptoms, improving CT images and viral conversion rates. Reported adverse events are mild. However, for certain biases in the included studies, and the need for further study on effective components of herbal medicine. Further large trials with better randomized design are warranted to definite a more definite role of herbal medicine.

Glucosamine Interferes With Myelopoiesis and Enhances the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells.

Glucosamine (GlcN) is the most widely consumed dietary supplement and exhibits anti-inflammatory effects. However, the influence of GlcN on immune cell generation and function is largely unclear. In this study, GlcN was delivered into mice to examine its biological function in hematopoiesis. We found that GlcN promoted the production of immature myeloid cells, known as myeloid-derived suppressor cells (MDSCs), both in vivo and in vitro. Additionally, GlcN upregulated the expression of glucose transporter 1 in hematopoietic stem and progenitor cells (HSPCs), influenced HSPC functions, and downregulated key genes involved in myelopoiesis. Furthermore, GlcN increased the expression of arginase 1 and inducible nitric oxide synthase to produce high levels of reactive oxygen species, which was regulated by the STAT3 and ERK1/2 pathways, to increase the immunosuppressive ability of MDSCs. We revealed a novel role for GlcN in myelopoiesis and MDSC activity involving a potential link between GlcN and immune system, as well as the new therapeutic benefit.

Risk factors of intrahepatic biloma and secondary infection after thermal ablation for malignant hepatic tumors.

Objective: This study aimed to evaluate the risk factors of biloma formation and secondary infection after thermal ablation for malignant hepatic tumors. Patients and methods: A total of 58 patients with 68 bilomas after thermal ablation were recruited as the complication group, and 61 patients with 72 lesions without major complications were selected randomly as the control group. The potential risk factors for biloma formation were analyzed with the chi-square test and multivariate logistic regression analysis. To determine the optimum management method for biloma, patients with secondary infection were included for the subgroup analysis of risk factors. Results: A history of transcatheter arterial chemoembolization (TACE) treatment (odds ratio [OR]: 3.606, 95% confidence interval [CI]: 1.165-11.156, p = .026) and tumor location (OR: 37.734, 95% CI: 13.058-109.034, p = .000) were independent predictors of biloma formation. Among the 58 patients with biloma, 49 (84.5%) showed no symptoms (i.e., the asymptomatic group), while the remaining 9 (15.5%) developed symptoms related to secondary infections (i.e., the symptomatic group). There were significant differences in the history of biliary manipulation (p = .031) between the symptomatic and asymptomatic groups. Conclusion: A history of TACE treatment and the distance from the biliary tract were independent predictors of biloma formation after thermal ablation. Therefore, protecting the bile duct (i.e., cooling of the bile duct and combing thermal ablation with chemical ablation) should be considered for high-risk patients. Moreover, active monitoring and management should be performed for patients with bilomas who underwent biliary surgery before.

Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells.

BACKGROUND Jolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities. MATERIAL AND METHODS We used different concentrations of JA and JB (20 µg/ml, 40 µg/ml, 60 µg/ml, 80 µg/ml, and 100 µg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs). RESULTS We found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide. CONCLUSIONS Our results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.

Arabidopsis PLC2 is involved in auxin-modulated reproductive development.

Phospholipase C (PLC) is an enzyme that plays crucial roles in various signal transduction pathways in mammalian cells. However, the role of PLC in plant development is poorly understood. Here we report involvement of PLC2 in auxin-mediated reproductive development in Arabidopsis. Disruption of PLC2 led to sterility, indicating a significant role for PLC2 in reproductive development. Development of both male and female gametophytes was severely perturbed in plc2 mutants. Moreover, elevated auxin levels were observed in plc2 floral tissues, suggesting that the infertility of plc2 plants may be associated with increased auxin concentrations in the reproductive organs. We show that expression levels of the auxin reporters DR5:GUS and DR5:GFP were elevated in plc2 anthers and ovules. In addition, we found that expression of the auxin biosynthetic YUCCA genes was increased in plc2 plants. We conclude that PLC2 is involved in auxin biosynthesis and signaling, thus modulating development of both male and female gametophytes in Arabidopsis.

Sorafenib or sunitinib as postoperative adjuvant therapy for Chinese patients with locally advanced clear cell renal cell carcinoma at high risk for disease recurrence.

OBJECTIVE: To evaluate the efficacy and safety of targeted agents (sorafenib and sunitinib) as postoperative adjuvant therapy in Chinese patients with clear cell renal cell carcinoma (CC-RCC) who are at high risk for disease recurrence. MATERIALS AND METHODS: Forty-three patients treated at our center between December 2007 and December 2010 with locally advanced CC-RCC who were at a high risk for disease recurrence were enrolled into the study. The criteria for high risk of CC-RCC recurrence postoperatively were defined according to the Mayo Clinic stage, size, grade, and necrosis (SSIGN) score for CC-RCC. After radical nephrectomy, patients received either sorafenib (group A, n = 20) or sunitinib (group B, n = 23) and were followed up for at least 1 year to determine the efficacy and safety of the test products. The duration of maintenance targeted medication treatment was approximately 1 year. Group C consisted of 388 CC-RCC patients treated at our center between 1992 and 2007, who were at high risk for disease recurrence and who received no adjuvant therapy. RESULTS: The demography characteristics were similar among the 3 groups. The overall rate of recurrence in groups A and B was not different (15.0% and 17.4% (P > 0.05), respectively), which was lower than that of group C (38.7%, P < 0.05 compared with groups A and B). Disease-free survival (DFS) was longer in groups A and B (18.9 ± 5.9 months and 16.9 ± 6.1 months [P > 0.05], respectively), compared with group C (13.3 ± 7.2 months, P < 0.05 compared with groups A and B). The common adverse effects of targeted therapy included hand-foot syndrome, fatigue, diarrhea, taste disturbance, rash, hypertension, alopecia, stomatitis, neutropenia, nausea, pruritus, hypothyroidism in groups A and B. The adverse effects were mild in both groups and the incidence was not significantly different between groups A and B. CONCLUSIONS: Targeted adjuvant therapy postoperatively with sorafenib or sunitinib in patients with CC-RCC who are at a high risk for disease recurrence was well tolerated and effective in reducing the rate of CC-RCC recurrence in these patients. This study is an attempt to assess the utility of adjuvant tyrosine kinase inhibitors (TKIs) after surgery for renal carcinoma. The apparently improved outcomes, compared with a historical control population, are of sufficient interest to support the continuation of an ongoing randomized clinical trial to validate the hypothesis.