Pharmacological activity and clinical progress of Triptolide and its derivatives LLDT-8, PG490-88Na, and Minnelide: a narrative review.

Triptolide, a compound isolated from a Chinese medicinal herb, has potent antitumor, immunosuppressive, and anti-inflammatory properties. Due to its interesting structural features and diverse pharmacological activities, it has attracted great interest by the Society of Organic Chemistry and Pharmaceutical Chemistry. However, its clinical potential is greatly hampered by limited aqueous solubility and oral bioavailability, and multi-organ toxicity. In recent years, various derivatives of Triptolide have made varying degrees of progress in the treatment of inflammatory diseases, autoimmune diseases, and cancer. The most researched and potentially clinically valuable of them were (5R)-5-hydroxytriptolide (LLDT-8), PG490-88Na (F6008), and Minnelide. In this review, we provide an overview of the advancements made in triptolide and several of its derivatives' biological activity, mechanisms of action, and clinical development. We also summarized some prospects for the future development of triptolide and its derivatives. It is hoped to contribute to a better understanding of the progress in this field, make constructive suggestions for further studies of Triptolide, and provide a theoretical reference for the rational development of new drugs.

[Evaluation of severity and prognosis of acute pancreatitis by CT severity index and modified CT severity index].

Objectives: To explore the role of computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI) in assessing the severity of acute pancreatitis (AP) under the revised Atlanta classification (RAC) and predicting the clinical prognosis. Methods: Based on the prospectively entered AP database, the clinical data of consecutive adult AP inpatients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from January 2012 to December 2020 were retrospectively screened. The imaging data were independently evaluated by two radiologists and entered to the database to calculate the CTSI and MCTSI scores. Their relationship with the difference of RAC severity grade and clinical prognosis was analyzed. Compared with Acute Physiology and Chronic Health Assessment Ⅱ (APACHE Ⅱ) score, the receiver operating characteristic curve was used to evaluate the predictive value of CTSI and MCTSI scores for persistent organ failure and infectious pancreatic necrosis (IPN). Results: A total of 2 612 patients with AP, aged (50±15) years, were included in the study, including 1 547 males (59.2%) and 1 065 females (40.8%). According to RAC standard, AP was divided into 699 cases (26.8%) of mild pancreatitis (MAP), 1 098 cases (42.0%) of moderately severe pancreatitis (MSAP), and 815 cases (31.2%) of severe pancreatitis (SAP). MCTSI judged AP severity similarly to RAC, with 668 cases of MAP (25.6%), 1 207 cases of MSAP (46.2%) and 737 cases of SAP (28.2%), while CTSI judged SAP patients less(400 cases, 15.3%). The severity of AP determined by CTSI and MCTSI scores was significantly correlated with clinical prognosis (r=0.06-0.43, all P<0.05). Compared with APACHE Ⅱ score, CTSI had the highest area under the curve (AUC) for predicting IPN (AUC=0.85, 95%CI: 0.83-0.87), followed by MCTSI (AUC=0.82, 95%CI: 0.80-0.85). APACHE Ⅱ was more accurate in predicting persistent organ failure than CTSI and MCTSI scores,with AUC of 0.73 (95%CI: 0.71-0.75), 0.72 (95%CI: 0.70-0.74) and 0.72 (95%CI: 0.70-0.74), respectively. Conclusions: AP severity judged by MCTSI is consistent with RAC, and SAP patients judged by CTSI are less than RAC. CTSI and MCTSI are significantly correlated with clinical prognosis. CTSI and MCTSI have higher accuracy in predicting IPN, but lower accuracy in predicting persistent organ failure than APACHE Ⅱ.

Evaluation of the inhibitory effects of drugs on the growth of Babesia gibsoni using relative quantification real-time PCR.

To evaluate the inhibitory effects of drugs on the growth of Babesia gibsoni, relative quantification real-time PCR method was developed in this study. The 18S rRNA gene was used as a target gene for the 2-ΔΔCt method analysis. Additionally, chicken RNA was added to the parasitized blood before total RNA extraction. The chicken ß-actin gene was selected as an internal control gene for the 2-ΔΔCt method analysis. The 100 µL parasitized blood samples with different percentages of parasitized erythrocytes (PPEs) (3%, 1.5%, 0.75%, 0.375% and 0.1875%) were prepared for relative quantification of B. gibsoni. Regression analysis results revealed significant linear relationships between the relative quantification value and parasitemia. 18S rRNA gene expression was significantly decreased after treatment with diminazene aceturate and artesunate in vitro drug sensitivity test. This result suggested that this relative quantification real-time PCR method can be used to evaluate the effects of drug inhibition.

[Comparison of severity and clinical outcomes between hypertriglyceridemic pancreatitis and acute pancreatitis due to other causes].

OBJECTIVE: To investigate the difference in severity and clinical outcomes between hypertriglyceridemic pancreatitis (HTGP) and acute pancreatitis (AP) of other causes, and to analyze the correlation between the serum triglyceride (TG) level <24 h after onset and the disease severity. METHODS: Patients were selected from the AP database of the First Affiliated Hospital of Nanchang University, who were admitted between January 2005 and December 2013, aged ≥18 and ≤85 years, excluding pregnant or lactating women. Severity and etiology of AP were classified according to the latest relevant guidelines. The severity and clinical outcomes of HTGP patients (HTGP group) were compared with those of patients with AP of other causes (non-HTGP group). Among the HTGP patients, those admitted within 24 hours of onset were selected for comparison of serum TG levels on the first day of hospitalization day among patients with mild, moderate, and severe HTGP, and the correlation between the serum TG level and the severity was analyzed. RESULTS: Altogether 3 558 AP patients were selected, of which 623 (17.5%) were HTGP, and 2 935 (82.5%)were non-HTGP patients. Compared with the non-HTGP group, the HTGP group had higher incidence of pancreatic necrosis (28.3% vs 18.1%), infected pancreatic necrosis (6.1% vs 3.7%), organ failure(35.8% vs 29.1%), and persistent organ failure(24.4% vs 16.5%), with all the differences being statistically significant (all P<0.01). The mortality and average stay in intensive care unit were also higher in the HTGP group than in the non-HTGP group (all P<0.05). There were 291 patients with HTGP who were admitted to hospital within 24 hours of onset. The serum TG levels <24 h after onset were (9.38±9.00) mmol/L, (11.90±9.02) mmol/L, and (16.47±11.75) mmol/L in patients with mild, moderate, and severe HTGP, respectively (P<0.01). Spearman's correlation analysis showed a positive correlation between TG level <24 h after onset and disease severity (r=0.26, P<0.01). CONCLUSIONS: Compared with AP of other causes, HTGP patients have more severe clinical course and worse clinical outcomes. The serum TG level within 24 hours of onset may be positively correlated with the severity of HTGP.

Late Permian marine ecosystem collapse began in deeper waters: evidence from brachiopod diversity and body size changes.

Analysis of Permian-Triassic brachiopod diversity and body size changes from different water depths spanning the continental shelf to basinal facies in South China provides insights into the process of environmental deterioration. Comparison of the temporal changes of brachiopod diversity between deepwater and shallow-water facies demonstrates that deepwater brachiopods disappeared earlier than shallow-water brachiopods. This indicates that high environmental stress commenced first in deepwater settings and later extended to shallow waters. This environmental stress is attributed to major volcanic eruptions, which first led to formation of a stratified ocean and a chemocline in the outer shelf and deeper water environments, causing the disappearance of deep marine benthos including brachiopods. The chemocline then rapidly migrated upward and extended to shallow waters, causing widespread mass extinction of shallow marine benthos. We predict that the spatial and temporal patterns of earlier onset of disappearance/extinction and ecological crisis in deeper water ecosystems will be recorded during other episodes of rapid global warming.

Controls on body size during the Late Permian mass extinction event.

This study examines the morphological responses of Late Permian brachiopods to environmental changes. Quantitative analysis of body size data from Permian-Triassic brachiopods has demonstrated significant, directional changes in body size before, during and after the Late Permian mass extinction event. Brachiopod size significantly reduced before and during the extinction interval, increased for a short time in more extinction-resistant taxa in the latter stages of extinction and then dramatically reduced again across the Permian/Triassic boundary. Relative abundances of trace elements and acritarchs demonstrate that the body size reductions which happened before, during and after extinction were driven by primary productivity collapse, whereas declining oxygen levels had less effect. An episode of size increase in two of the more extinction-resistant brachiopod species is unrelated to environmental change and possibly was the result of reduced interspecific competition for resources following the extinction of competitors. Based on the results of this study, predictions can be made for the possible responses of modern benthos to present-day environmental changes.

Effects on protein and mRNA expression levels of p53 induced by fluoride in human embryonic hepatocytes.

We investigated the effects of protein and mRNA expression levels on p53 induced by fluoride in human embryo hepatocyte L-02 cells. The protein and mRNA levels of p53 in L-02 cells were measured after in vitro cultured L-02 was exposed to sodium fluoride at different doses (40, 80, and 160 microg/ml) for 24 h. The results showed that the cell survival rate of L-02 cells in the high dose fluoride group was significantly lower than that of the control group. The protein expression levels of p53 in the middle and high dose fluoride group were significantly higher than in the control group and elevated with increasing fluoride concentration. The mRNA expression levels of p53 in the fluoride groups were markedly higher than in the control group. The mRNA expression level of p53 in the high dose fluoride group was however lower compared to the middle dose fluoride group, but similar to the low dose fluoride group. These finding suggest that fluoride can decrease the L-02 cells survival rate and induce protein and mRNA expressions of p53; however, there is no consistency between the protein expression level of p53 and the mRNA expression level.