Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.

Cantharidin (CTD), a natural compound derived from Mylabris, is widely used in traditional Oriental medicine for its potent anticancer properties. However, its clinical application is restricted due to its high toxicity, particularly towards the liver. This review provides a concise understanding of the hepatotoxic mechanisms of CTD and highlights novel therapeutic strategies to mitigate its toxicity while enhancing its anticancer efficacy. We systematically explore the molecular mechanisms underlying CTD-induced hepatotoxicity, focusing on the involvement of apoptotic and autophagic processes in hepatocyte injury. We further discuss the endogenous and exogenous pathways implicated in CTD-induced liver damage and potential therapeutic targets. This review also summarizes the structural modifications of CTD derivatives and their impact on anticancer activity. Additionally, we delve into the advancements in nanoparticle-based drug delivery systems that hold promise in overcoming the limitations of CTD derivatives. By offering valuable insights into the hepatotoxic mechanisms of CTD and outlining potential avenues for future research, this review contributes to the ongoing efforts to develop safer and more effective CTD-based therapies.

Alterations in gut microbiota are related to metabolite profiles in spinal cord injury.

Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8-T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.

Four new caffeoylgluconic acid positional isomers from the fruits of Evodia rutaecarpa.

Four new compounds, 4-O-trans-caffeoylgluconic acid (1), 2-O-trans-caffeoylgluconic acid (2), 3-O-trans-caffeoylgluconic acid (3), 5-O-trans-caffeoylgluconic acid (4), together with three known ones including 6-O-trans-caffeoylgluconic acid (5), neochlorogenic acid (6), chlorogenic acid (7) were obtained from the fruits of Evodia rutaecarpa. Their structure elucidation was achieved by the methods of spectroscopic analyses, including HR-ESI-MS, NMR, and by comparison with literatures. The hepatotoxicity of compounds 1-3 was evaluated by CCK-8 method. [Formula: see text].

[Research,evaluation,industry status and development strategy of traditional Chinese medicine functional food].

With the development of social economy,people's demand for health services is growing rapidly. As health resource with Chinese characteristics,health food containing Chinese materia medica have broad prospect and great market space for development.However,at present,there are still many problems of health food containing Chinese materia media in the research,development,evaluation and market application. In addition,due to lack of theoretical support of traditional Chinese medicine(TCM) in the research and development of health food containing Chinese materia media,blurred boundaries between health food containing Chinese materia media and other health products as well as TCM are present,lacking of TCM characteristics. In the evaluation process of health food containing Chinese materia media,the construction of functional food laws,regulations and evaluation norms is relatively lagging behind,which can't meet the needs of health food containing Chinese materia media research and development,severely restricting the development of health food containing Chinese materia media. Based on the research and evaluation of health food containing Chinese materia media,the existing problems were reviewed and the reasons for the deficiencies were analyzed in this paper. Guided by the theory of TCM,based on the constitution identification in TCM,and combined with modern scientific and technological means,a new research and development mode of functional food was put forward in this paper to distinguish health food containing Chinese materia media from TCM as well as general health products. Nevertheless,we should ensure the vitality of Chinese medicine health products with original thinking and scientific and technological connotations,and accelerate the harmonious,rapid and sustainable development of Chinese medicine health industry.

[Current evaluation situation and research strategies on enhanced immune function of health food containing Chinese materia medica].

At present,the function evaluation of health food containing Chinese materia medica is in lack of theoretical support of Chinese medicine,which can't reflect the function characteristics,dose-effect relationship and mechanism of functional food. What' s more,the evaluation technology of health food containing Chinese materia medica is relatively lagging behind and has been abolished now,which seriously restricts the development of health food containing Chinese materia medica industry. The proportion of health food containing Chinese materia medica with enhancing immune function is the highest among approved products,which is up to 30.33%. By collecting,analyzing and digging the current evaluation situation of enhancing immune function of health food containing Chinese materia medica,this paper has shown that there is no difference between health food containing Chinese materia medica evaluation and other functional food evaluation. What's more,there is a lack of characteristics of traditional Chinese medicine(TCM). The technological means including evaluation of immune active substances is under-developed and the immune cell evaluation needs to be refined and improved urgently,restricting the development of health food containing Chinese materia medica industry. Therefore,the evaluation of the enhanced immune function of health food containing Chinese materia medica should be guided by health-preserving theory in TCM,and based on the identification of TCM constitution for its claim of health function. With TCM theory and modern scientific technological means,a new evaluation model for immune function enhancement of health food containing Chinese materia medica is put forward to distinguish it from other functional food and traditional medicines. Formulation of the evaluation technology and technical specifications suitable for health food containing Chinese materia medica can fundamentally ensure the healthy,orderly,fast and sustainable development of health food containing Chinese materia medica industry.

Elevated Tumor Necrosis Factor-a-induced Protein 8-like 2 mRNA from Peripheral Blood Mononuclear Cells in Patients with Acute Ischemic Stroke.

Background: Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel regulator of immunity and protects against experimental stroke. However, the expression and function of TIPE2 in patients with acute ischemic stroke has not been well demonstrated. Methods: A total of 182 consecutive patients with acute ischemic stroke and 40 healthy controls were included during November 2015 to June 2016. The mRNA levels of TIPE2, interleukin(IL)-1ß, IL-10, IL-6, nuclear factor(NF)-κß, activator protein(AP)-1, interferon(IFN)-γ and tumor necrosis factor(TNF)-α from peripheral blood mononuclear cells were determined using real time quantitative reverse transcriptase polymerase chain reaction. The severity of stroke was assessed using the National Institutes of Health Stroke Scale (NIHSS) score. Results: The median mRNA levels of TIPE2, TNF-α, AP-1, IFN-γ and NF-κß in patients with acute ischemic stroke were significantly higher than healthy controls (all P<0.001, respectively). Of note, TIPE2 mRNA showed an increasing trend on a time-dependent manner after the onset of stroke. Furthermore, TIPE2 mRNA was negatively associated with lesion volumes (r=-0.23, P<0.01), NIHSS(r=-0.15, P<0.05), TNF-α(r=-0.33,P<0.001), AP-1(r=-0.28,P<0.001), IFN-γ (r=-0.16, P<0.05) and NF-κß (r=-0.13, P<0.05), but positively associated with IL-6(r=0.14, P<0.05) and IL-10(r=-0.31, P<0.001). Hierarchy cluster analysis showed that TIPE2 mRNA has nearest membership with TNF-α, followed by IL-6, NF-κß, AP-1, IL-10, IL-1ß and IFN-γ. In addition, TIPE2 mRNA in survivals (n=149) was significantly higher than nonsurvivals (n=33) (P<0.001), and showed a great odd ratio (0.52, 95% confidence interval: 0.349-0.760, P<0.001) on 3-month mortality. Conclusions: TIPE2 mRNA contributed to the immune response of stroke and might be a potential biomarker for the mortality of acute ischemic stroke.

Peripheral tumor necrosis factor-a-induced protein 8-like 2 mRNA level for predicting 3-month mortality of patients with acute ischemic stroke.

Tumor necrosis factor-a-induced protein 8-like 2 (TIPE2) is a novel negative regulator for maintaining immune homeostasis. This study aimed to investigate TIPE2 mRNA in peripheral blood mononuclear cells for predicting 3-month functional outcomes and mortality of patients with acute ischemic stroke. A total of 182 consecutive patients were prospective collected, and there were 55 (30.2%) patients with unfavorable outcome and 33 (18.1%) patients died at the end of 3 months. The area under the operating characteristic curve (AUC) for TIPE2 mRNA was 0.810 (95% CI 0.733-0.886) for mortality and 0.740 (95% CI 0.662-0.818) for unfavorable outcome. The model incorporating National Institutes of Health Stroke Scale (NIHSS) plus TIPE2 showed significantly (P = 0.04) increased discrimination power (AUC = 0.925, 95% CI 0.874-0.976) for mortality than NIHSS (AUC = 0.882, 95% CI 0.833-0.932). Furthermore, NIHSS plus TIPE2 showed a significant improvement of both integrated discrimination index (IDI) and net reclassification index (NRI) as compared with NIHSS (IDI = 0.224, 95% CI 0.150-0.299, P < 0.001; NRI = 1.119, 95% CI 0.810-1.429, P < 0.001). The pruned time-dependent tree analysis showed that patients with NIHSS ≥ 5.5 and TIPE2 mRNA < 5.2 had rather high 3-month mortality. In conclusion, TIPE2 mRNA improved the diagnostic value of NIHSS score, and patients with NIHSS ≥ 5.5 and TIPE2 mRNA < 5.2 had high 3-month mortality.

[Tidal breathing pulmonary function after treatment in neonates with respiratory distress syndrome].

OBJECTIVE: To investigate the pulmonary function after treatment in neonates with respiratory distress syndrome (RDS) at varying disease severity levels and different gestational ages. METHODS: A total of 107 neonates with RDS were divided into <34 weeks group (65 neonates), late preterm group (21 neonates), full-term group (21 neonates). Another 121 non-RDS children were enrolled as the control group. According to the severity of RDS, the RDS neonates were divided into mild RDS group (grades 1 and 2; 76 neonates), and severe RDS (grades 3 and 4; 21 neonates). The tidal breathing pulmonary function was measured at a corrected gestational age of 44weeks. RESULTS: The pulmonary function parameters showed no significant differences across the groups of RDS neonates of different gestational ages; the tidal volume per kilogram of body weight (VT/kg) showed no significant difference between the RDS and non-RDS groups, while the RDS group had significantly higher ratio of time to peak tidal expiratory flow to total expiratory time (tPTEF/tE) and ratio of volume to peak tidal expiratory flow to total expiratory volume (vPTEF/vE) than the non-RDS group of the same gestational age (P<0.05). At a corrected gestational age of 44 weeks, the two groups of neonates with varying severity levels of RDS had significantly lower tPTEF/tE and vPTEF/vE than the control group (P<0.05), and tPTEF/tE and vPTEF/vE tended to decrease with the increasing severity level of RDS. CONCLUSIONS: Neonates with RDS have significantly decreased pulmonary function than those without RDS. At a corrected gestational age of 44 weeks, the tidal breathing pulmonary function in neonates with RDS is not associated with gestational age, but is associated with the severity of RDS.

[Research on rat models of acute liver injury with syndrome of liver depression and spleen deficiency].

This paper aimed to establish animal models which are suitable for the activity found, efficacy evaluation of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency and new drug research and development based on corresponding of formula and syndrome. The symptoms that are suitable for evaluating the rat models of acute liver injury with syndrome of liver depression and spleen deficiency were extracted according to the evolution rule of the etiology and pathogenesis in traditional Chinese medicine and the modern pathological mechanism. Xiaoyao pill and silibin meglumine tablets were used as drug counter evidence for models in accordence with the principle of consistence of prescription and syndrome. Rats model were fed with high-lipid and low-protein fodder of different proportion and induced by intraperitoneal injection with pig serum, intragastric administration with edible alcohol once a day for 7 days. Daily record of body weight, daily food intake and daily water intake were conducted day after day in experimental session. Symptoms were also observed and evaluated by score at the same time. The contents of ALT, AST, PA, TBIL and TBA in serum were detected and histopathological changes of liver were checked at the ending of experiment. Obvious acute liver injury occurred to all rats in model groups at 1 week following model induction. Both main symptoms and secondary symptoms were consistent with syndrome manifestation of liver depression and spleen deficiency. Compared with normal control group, the activity of ALT,AST and contents of TBIL,TBA in serum increased and the content of PA decreased. Liver tissue pathological morphology showed inflammatory cells infiltration, eosinophilic or eosinophilic adipose change in hepatocytes of rats in model groups. All the above lesions manifestation could be improved by drug counterevidence. By the disproof of medicine, rat models of acute liver injury with syndrome of liver depression and spleen deficiency could be induced by fed with high-lipid and low-protein fodder which contained 89.5% cornstarch, 10% lard and 0.5% cholesterol, intraperitoneal injected with pig serum, intragastric administrated with edible alcohol for 7 days. The rat models with a low mortality could be induced in a short time and animal status were similar to syndrome performance of patients. So the rats models are suitable for the activity found, efficacy evaluation and drug discovery of herbs resistant to acute liver injury with syndrome of liver depression and spleen deficiency, and also can be used in the research of correlation between prescription and syndrome and its mechanism.

[Measurement of tidal breathing pulmonary function in premature infants with different gestational ages].

OBJECTIVE: To investigate the characteristics of the tidal breathing pulmonary function in premature infants with different gestational ages. METHODS: A total of 75 premature infants were classified into three groups according to their gestational ages: <32 weeks, 32-33(+6) weeks and 34-36(+6) weeks. Fifty-five full-term infants (39-40 weeks group) were selected as the control group. All infants were given the tidal breathing pulmonary function test at 3-5 days after birth. Moreover, all infants were given the tidal breathing pulmonary function test again at 40 weeks of the corrected gestational age. RESULTS: At 3-5 days after birth, the three groups of premature infants had significantly lower inspiratory time, time to peak tidal expiratory flow (tPTEF), and ratio of tPTEF to total expiratory time (tPTEF/tE) than the control group (P<0.05). The parameter values of the tidal breathing pulmonary function were lower when the gestational age was lower. Even at 40 weeks of the corrected gestational age, the three groups of premature infants still had significantly lower tPTEF and tPTEF/tE than the control group (P<0.05). CONCLUSIONS: The tidal breathing pulmonary function of neonates is influenced by the gestational age. The tidal breathing pulmonary function of premature infants is obviously impaired, and the lower the gestational age, the more obvious the impairment.

[Etiology and prevention of neonatal pneumothorax].

OBJECTIVE: To investigate the risk factors and preventative measures for neonatal pneumothorax. METHODS: Retrospective analysis was performed on the clinical data of 2286 neonates who were hospitalized in the neonatal intensive care unit between October 2010 and November 2011, and a case-control study was conducted to analyze the risk factors and preventative measures for neonatal pneumothorax. RESULTS: The incidence of pneumothorax among the neonates was 1.57% (36/2286), and it was significantly higher in full-term infants than in preterm infants (23/1033 vs 13/1253, P=0.023). Logistic regression analysis indicated that cesarean section, neonatal respiratory distress syndrome (NRDS), wet lung, pneumonia and mechanical ventilation were the independent risk factors for neonatal pneumothorax (odds ratios=7.951, 6.090, 7.898, 6.272 and 4.389; P<0.05 for all). The higher the peak inspiratory pressure (PIP) during mechanical ventilation, the higher the incidence of neonatal pneumothorax (P<0.001). Pulmonary surfactant reduced the incidence of pneumothorax among neonates with NRDS (2.9% vs 10.1%; P=0.006). CONCLUSIONS: Neonatal pneumothorax occurs mostly in full-term infants. Cesarean section, NRDS, wet lung, pneumonia and mechanical ventilation are closely associated with neonatal pneumothorax. Strict management of indications for cesarean section, keeping PIP at a low level during mechanical ventilation, and use of pulmonary surfactant are helpful in preventing neonatal pneumothorax.