Scutellaria baicalensis: a promising natural source of antiviral compounds for the treatment of viral diseases / 中国天然药物

Viruses, the smallest microorganisms, continue to present an escalating threat to human health, being the leading cause of mortality worldwide. Over the decades, although significant progress has been made in the development of therapies and vaccines against viral diseases, the need for effective antiviral interventions remains urgent. This urgency stems from the lack of effective vaccines, the severe side effects associated with current drugs, and the emergence of drug-resistant viral strains. Natural plants, particularly traditionally-used herbs, are often considered an excellent source of medicinal drugs with potent antiviral efficacy, as well as a substantial safety profile. Scutellaria baicalensis, a traditional Chinese medicine, has garnered considerable attention due to its extensive investigation across diverse therapeutic areas and its demonstrated efficacy in both preclinical and clinical trials. In this review, we mainly focused on the potential antiviral activities of ingredients in Scutellaria baicalensis, shedding light on their underlying mechanisms of action and therapeutic applications in the treatment of viral infections.

Potential health benefits of resveratrol: a pharmacokinetics-caused conundrum / 中国临床药理学与治疗学

Resveratrol (3, 5, 4'-trihydroxy-trans-stilbene) was first identified from white hellebore (Veratrum grandiflorum) root and began to attract interest when its presence in red wine and cardiovascular activities were reported, leading to speculation of its contribution to the 'French paradox'. Besides the cardiovascular protection, potential health benefits of resveratrol include calorie restriction-like effects, cancer prevention and adjunctive therapy, and neuroprotection. In order to achieve translational applications of these potential benefits, pharmacokinetic research was performed for plasma pharmacokinetics and related disposition of orally dosed resveratrol. This paper summarizes the known human pharmacokinetic characteristics of resveratrol after oral administration and various attempts to improve its systemic exposure level from the perspectives of systemic exposure and in vivo process. However, available pharmacokinetic data of resveratrol has raised conundrums that limit translating potential benefits to clinics: (1) differences between the unchanged resveratrol used in bioactivity studies and its major circulating forms (i.e., metabolites) after dosing; (2) resveratrol's test concentrations used to exert in vitro bioactivities related to the benefits significantly higher than the compound's clinically achievable concentrations; (3) resveratrol's concentrations achievable (estimated from the pharmacokinetics) from doses used to produce in vivo efficacy significantly lower than the effective concentrations found in studies of related action mechanism (suggesting unreliability of test mechanism). In the last part of this review, we provide recommendations for future pharmacokinetic investigations of resveratrol, including a more systematic investigation of systemic exposure to resveratrol metabolites, their access to in vivo loci responsible for the benefits, and their disposition in target cells; an investigation of colon-luminal exposure to resveratrol and its metabolites for accessing colonic microbiota; and a multi-compound pharmacokinetic investigation of red wine.

Tripodalsporormielones A-C, unprecedented cage-like polyketides with complex polyvdent bridged and fused ring systems

A chemical investigation on

Study on the mechanism of MALAT1 targeting miR-142-3p in ovarian cancer chemotherapy resistance / 国际肿瘤学杂志

Objective:To study the mechanism of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) targeting microRNA-142-3p (miR-142-3p) in ovarian cancer chemotherapy resistance.Methods:A total of 80 ovarian cancer tissues and paired normal tissues were collected in Shaanxi Provincial People′s Hospital from February 2016 to February 2019. The relative expression levels of MALAT1 and miR-142-3p in ovarian cancer tissues and paired normal tissues were detected by real-time fluorescence quantitative polymerase chain reaction (PCR), and the correlation between MALAT1 and miR-142-3p was analyzed. The effects of abnormal expressions of MALAT1 and miR-142-3p on proliferation and chemotherapy sensitivity of 5-fluorouracil (5-FU) and cisplatin of ovarian cancer Hey cells were verified by CCK-8 assay. Dual luciferase reporter gene experiment was used to detect the targeted relationship between miR-142-3p and MALAT1 (Hey cells were divided into four groups: MALAT1 wt, MALAT1 wt+ miR-142-3p mimic, MALAT1 mut, MALAT1 mut+ miR-142-3p mimic). RNA immunoprecipitation assay was use to confirm the binding site of MALAT1 and miR-142-3p.Results:In the ovarian cancer tissues and paired normal tissues, the relative expression levels of MALAT1 were 0.000 52 (0.002 56) and 0.000 47 (0.000 89), with a statistically significant difference ( Z=2.365, P=0.018); the relative expression levels of miR-142-3p were 0.001 19 (0.002 69) and 0.001 61 (0.008 48), with a statistically significant difference ( Z=2.935, P=0.003). The relative expression level of MALAT1 was negatively correlated with miR-142-3p in the ovarian cancer tissues ( r=-0.474, P<0.001). The relative expression level of miR-142-3p in the miR-142-3p mock group was statistically lower than that of MALAT1+ miR-142-3p mimic group (0.004 18±0.001 24 vs. 0.006 51±0.000 28; t=3.174, P=0.017). The relative fluorescence concentrations of MALAT1 wt group and MALAT1 wt+ miR-142-3p mimic group were 2.27±0.86 and 31.10±6.05 respectively, with a statistically significant difference ( t=8.172, P<0.001). After 48, 72 and 96 hours of ovarian cancer Hey cells being transfected with MALAT1 overexpression plasmid, the absorbance ( A) values of cells in the MALAT1 overexpression group were significantly greater than those in the control group (0.522±0.021 vs. 0.433±0.021; 0.644±0.012 vs. 0.544±0.051; 0.887±0.055 vs. 0.698±0.042), with statistically significant differences (all P<0.05). After MALAT1 being overexpressed in Hey cells, at 0.10 ng/μl concentration of 5-FU, the proliferation rate of cells in the overexpression group was significantly faster than that in the control group (0.615±0.036 vs. 0.506±0.042; t=4.432, P=0.002), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU showed the same trends (all P<0.05). At 0.01 ng/μl concentration of cisplatin, the proliferation rate of cells in the overexpression group was significantly faster than that in the control group (0.777±0.015 vs. 0.733±0.039; t=2.355, P=0.023), and the cells at 0.10, 1.00, 10.00, 100.00 ng/μl concentrations of cisplatin showed the same trends (all P<0.05). After miR-142-3p being overexpressed in Hey cells, at 0.10 ng/μl concentration of 5-FU, the proliferation rate of cells in the overexpression group was significantly slower than that in the control group (0.512±0.051 vs. 0.744±0.119; t=4.028, P=0.004), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU showed the same trends (all P<0.05). At 0.10 ng/μl concentration of cisplatin, the proliferation rate of cells in the overexpression group was significantly slower than that in the control group (0.520±0.043 vs. 0.674±0.096; t=3.441, P=0.009), and the cells at 1.00, 10.00, 100.00 ng/μl concentrations of cisplatin showed the same trends (all P<0.05). After ovarian cancer Hey cells being treated with 0.10, 1.00, 10.00, 100.00 ng/μl concentrations of 5-FU and cisplatin, the proliferation rates of cells in the MALAT1 overexpression group, MALAT1+ miR-142-3p group and control group showed statistically significant differences (all P<0.05). Further pairwise comparisons revealed that the proliferation rates of cells in the MALAT1+ miR-142-3p group were significantly slower than those in the MALAT1 overexpression group (all P<0.05). Conclusion:MALAT1 can reduce the sensitivity of ovarian cancer cells to 5-FU and cisplatin by targeted miR-142-3p, leading to chemotherapy resistance of ovarian cancer.

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

New Discussion on the Pathological Mechanism of Parkinson's Disease: Oxidative Death of Dopaminergic Neurons-Ferroptosis and Oxytosis / 世界科学技术-中医药现代化

The loss of dopaminergic neurons and the decreased release of dopamine neurotransmitters in the substantia nigra pars compacta are the main pathological mechanisms leading to Parkinson 's disease (PD) in clinical research. Under the combined influence of genes and environment, there are many death mechanisms of dopaminergic neurons. Current research suggests that apoptosis, necrosis and autophagic death all participate in the death of dopaminergic neurons, but these deaths are not sufficient to explain their pathological processes and mechanisms. Ferroptosis is a newly discovered iron-dependent cell death pathway characterized by increased iron load and accumulation of large amounts of lipid peroxides. These characteristics are highly consistent with the clinical molecular characteristics of the brain in PD patients. In addition, there is evidence that ferroptosis and oxytosis (observed in nerve cells 30 years ago) have a high degree of similarity in signal regulation, and they may represent the same form of programmed cell death. This review discusses the current advances of ferroptosis death pathway in PD, and briefly discusses the possibilities for ferroptosis and oxytosis as the same type of cell death. The elucidation of the death pathway and mechanism of dopaminergic neurons can provide a fundamental theoretical basis for the development of anti-PD drugs.

The latent infection of HSV-1 and stress-induced reactivation / 中国药理学通报

Herpes simplex virus type Ⅰ(HSV-1) is a common pathogen, and human is the only natural host of it.Following a period of lytic replication in epithelial cells, HSV-1 enters axon terminals of sensory neurons and then travels via retrograde transport to the sensory ganglia where latency can be established.Upon the stimulation of some stressors, the latent virus can reactivate, leading to recurrent diseases.Therefore, to clarify the mechanism of HSV-1 latent infection and stress-induced reactivation will offer new insights into the prevention, treatment and control of HSV-1 infection.In this review, we describes the mechanisms underlying HSV-1 latent infection and stress-induced reactivation.

Suture ligation and injection of PLE in the treatment of large venous malformations in oral and maxillofacial region / 实用口腔医学杂志

15 cases of large venous malformations in oral and maxillofacial region involving in multiple anatomical sites were treated by suture ligation and injection of pingyangmycin oleum iodisatum emulsion(PLE) for 2-5 times.Treatment effect of grade Ⅳ was observed in 12 cases,grade Ⅲ in 3 cases.No severe systemic adverse reaction and no local adverse reation were obseved in all cases.Suture ligation and PLE injection can enhance the therapeutic effect and reduce the adverse reactions in the treatment of large venous malformations of the oral and maxillofacial region.

Sirtuins in stem cell regulation:roles and prospects / 中国组织工程研究

BACKGROUND:Efficacy of stem cel therapy is considerably influenced by oxidative stress. Sirtuin (SIRT) family of mammals is an important deacetylation and antioxidant enzyme that can regulate endogenous antioxidant activities in stem cel s and cel cycle related signaling pathways to reduce the damage and enhance the viability of stem cel s. OBJECTIVE:To review the regulating function and mechanism of SIRT family. METHODS:A computer-based search of Web of Science, PubMed and CNKI from 1990 to 2015 was performed for relevant articles about SIRT and stem cel oxidative stress, using the key words of“SIRT, stem cel , oxidative stress, molecular mechanisms”in English and Chinese, respectively. After eliminating literatures which have poor authority or have similar contents, 55 articles were involved. RESULTS AND CONCLUSION:NAD+-dependent SIRT family is the key enzyme for deacetylation of histones and other proteins. It plays vital regulation roles in metabolism, genomic stability, DNA damage/repair, and chromatin remodeling/stress reaction. Progress in the SIRT-targeted stem cel research wil definitely provide more clues for clinical stem cel transplantation therapy.

Study on an Exoskeleton Hand Function Training Device / 生物医学工程学杂志

Based on the structure and motion bionic principle of the normal adult fingers, biological characteristics of human hands were analyzed, and a wearable exoskeleton hand function training device for the rehabilitation of stroke patients or patients with hand trauma was designed. This device includes the exoskeleton mechanical structure and the electromyography (EMG) control system. With adjustable mechanism, the device was capable to fit different finger lengths, and by capturing the EMG of the users' contralateral limb, the motion state of the exoskeleton hand was controlled. Then driven by the device, the user's fingers conducting adduction/abduction rehabilitation training was carried out. Finally, the mechanical properties and training effect of the exoskeleton hand were verified through mechanism simulation and the experiments on the experimental prototype of the wearable exoskeleton hand function training device.

Role of mitochondrial damage and repair in Parkinson′s disease / 中国药理学通报

Parkinson’ s disease ( PD) is a common disease in central nervous system, for which an effective treatment has yet to be found. The causes of PD include genetic, environmental, aging factors, etc. There is a common factor which can lead to the degeneration of dopaminergic neurons in the substantia:mito-chondrial damage and repair. This paper has summarized the en-vironmental and genetic factors that can cause mitochondrial damage in dopaminergic neurons, and outlined several mitochon-drial repairing pathways ( such as mitophagy) in the treatment of PD. It also analyzes the research situation of utilizing natural medicine in the therapy of PD from the perspective of the mito-chondrial protection.

Analysis of the current situation the oral medical interns' awareness on occupation safety behavior in college / 华西口腔医学杂志

<p><b>OBJECTIVE</b>This study aims to determine the awareness oral medical interns about occupation safety protection of knowledge and to present a scientific basis for perfecting the occupation safety education system and standard protection behavior.</p><p><b>METHODS</b>A self-designed questionnaire that used a retrospective questionnaire survey on 425 stomatological interns, scoring, and statistical analysis of the survey were performed. The questionnaire included occupation safety prevention knowledge, behavior cognitive, and protective behavior, among others.</p><p><b>RESULTS</b>The questionnaire recovery rate was 100%, and the average scores of the prevention knowledge and behavior cognitive were 4.55 ± 0.91 and 4.40 ± 1.05, respectively. More than 90% interns can conduct the conventional protection, and less than 40% can perform special protection. For the item "occupation safety protection knowledge", the scores of three grade III hospitals were higher than that of stomatological hospitals and second level of first-class hospitals; the difference was statistically significant (P < 0.001). For the items "behavior cognition" and "protective behavior", the scores of the second level of first-class hospitals were lower than those of grade III hospitals and stomatolgical hospitals (P < 0.001). The second level of first-class hospitals was relatively poor in safety protection knowledge, behavioral cognitive, and protection behavior. The average score was higher for than for boys in the three contents, and the average score of interns accepting pre-job training was higher than those rejected; the difference was statistically significant (P < 0.001).</p><p><b>CONCLUSION</b>The occupation safety knowledge of oral medical interns is not sufficient, and the protective behavior is poor. Schools and hospitals should strengthen the intern occupation safety and protection education and improve the status of occupation safety behavior.</p>

Clinical observation on the treatment of infant thrush by external use of chinese medicine / 实用口腔医学杂志

41 cases of infant thrush in observation group were treated by 10% rhubarb decoction wipe on the affected area followed by pow-dered “alum 3 +goldthread 2 +borneol 1”coating;41 cases in the control group were treated by 1% ~2% baking soda scrub on the affect-ed area followed by glycerol wipe containing 50 000 to 100 000 units/ml of nystatin.The efficiency was 95.12%(39 /41)and 75.61%(31 /41)in observation and control groups respectively(P <0.05).The external use of chinese medicine is effective in the treatment of in-fant thrush.

Theacrine ameliorates high fat diet induced hepatic steatosis in mice via SirT3/AMPK/ACC pathway / 中国药理学通报

Aim To investigate the effects and mecha-nisms of theacrine on high fat diet induced hepatic steatosis in mice. Methods The C57BL/6J mice were fed with high fat diet for consecutive 17 weeks to induce hepatic steatosis and given a treatment of theac-rine for 6 weeks. The liver sections were stained with H&E or Sudan IV, and hepatic TG was determined by commercial analysis kits. Expression of SirT3 and phosphorylation of AMPK and ACC were measured by Western blot. Compound C was used to inhibit the phosphorylation of AMPK in HepG2 cells, and the ex-pressions of proteins were determined after the cells were treated with theacrine. Results Theacrine sig- nificantly decreased hepatic TG content and ameliora-ted hepatic steatosis in mice. Expression of SirT3 and phosphorylation of AMPK and ACC were up-regulated, respectively. And theacrine still could activate SirT3 and up-regulate the phosphorylation of ACC whatever AMPK was inhibited. Conclusions The activation of ACC by theacrine depends on the phosphorylation of AMPK, but the activation of SirT3 by theacrine is in-dependent of the phosphorylation of AMPK. Theacrine ameliorates high fat diet induced hepatic steatosis in mice probably via SirT3/ AMPK/ ACC pathway.

Inhibition effects of tea flower extract on glucose absorption in experimental glucose tolerance mice / 国际药学研究杂志

Objective To study the inhibitory effects of tea flower extract(TFE) onα-glucosidase and glucose intestinal absor-ption. Methods Three different postprandial hyperglycemia models (2 g/kg glucose, 4 g/kg sucrose, and 6 g/kg starch) were used, with 8 mice in each group. Oral administration of 150 or 300 mg/kg of TFE, 6.25 mg/kg of acarbose, or water was performed on mice 1 day and 30 mins before the oral administration of 2 g/kg glucose, 4 g/kg sucrose, and 6 g/kg starch at 10 ml/kg of body weight. Blood glucose levels were analyzed chronologically to evaluate the effect of TFE. In vitro studies were also performed to study the inhibitory effects of TFE on α-glucosidase and small intestinal mucosa glycosidase. Results Neither TFE nor acarbose had significant influence in glucose-treated mice. However, there was a significant decrease in the postprandial blood glucose 20 min after sucrose administration (P<0.05), and 20 min and 40 min after starch administration (P<0.05). TFE also significantly inhibited the activities ofα-glucosidase of small intestinal mucosa, with 18.8%and 31.1%by 150 and 300 mg/kg TFE. The in vitro IC50 of TFE onα-glucosidase was 1.50 mg/ml. Conclusion TFE could effectively reduce the blood glucose level in hyperglycemic mice. Its mechanism might be related to the inhibitory effects ofα-glucosidase.

Effect of Vitex negundo var. heterophylla seeds ethanol extract (VSE) on mice model of immunological hepatitis and acute inflammation / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Vitex negundo var. heterophylla seeds ethanol extract(VSE) on immunological hepatitis and acute inflammation mice model.</p><p><b>METHOD</b>Hepatic function in the immunological liver injury model was evaluated by assessing the levels of ALT in plasma, and the content of MDA, ORAC, NO and iNOS mRNA in liver tissues. VSE effect on the acute inflammation caused by croton oil and carrageenan was observed.</p><p><b>RESULT</b>Compared to the model group, 125 and 500 mg x kg(-1) VSE could inhibit the activities of ALT in mice plasma, and enhanced levels of ORAC and decreased levels of MDA and modulated levels of NO in liver tissues. Meanwhile, VSE could ameliorate the ear swelling induced by croton oil and reduced the thickness of mice hind paw induced by carrageenan as well.</p><p><b>CONCLUSION</b>The results indicated that VSE exerted potential effects on immunological hepatitis and the mechanisms might be partly related to free radical scavenging activity and inhibit release of iNOS. VSE also showed partial effects on acute inflammation.</p>

Effects of Sarcandra glabra extract on immune activity in restraint stress mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the protective effect of Sarcandra glabra extract (SGE) on immune system in restrained mice.</p><p><b>METHOD</b>The male C57BL/6 mice were randomly divided into normal control group, stress control group, 125, 500 mg x kg(-1) SGE group. The spleen lymphocyte suspensions of each group were prepared. The parameters of spleen T cells subsets, NK cell and NKT cell proportion and number was detected by Flow cytometry.</p><p><b>RESULT</b>SGE regulated the balance of T cell subsets, increased the percent of NK cells and NKT cell proportion and number in restrained mice.</p><p><b>CONCLUSION</b>SGE has immunologic protective effect in restrained mice probably via the amelioration of immune cells proportion and number.</p>

Improvement of Guangdong Liangcha Granules on Restraint-stress-induced Perox idation in Genital Organs of Mice / 中药新药与临床药理

Objective To observe the improvement of Guangdong Liangcha Granules (GLG) on restraint-stress-induced peroxidation in genital organs of mice. Meth ods Mice models of peroxidation injury in genital organs were induced by 18-hou r restraint stress. Testicular and ovarian malondialdehyde (MDA) level was detec ted by thiobarbituric acid method,glutathione (GSH) content by HPLC,xanthine o xidase (XOD) and GSH-PX activities by colorimetric method,nitric oxide (NO) co ntent by Griess chemical method and oxygen radical absorbance capacity (ORAC) by enzyme-linked fluorescent immunoassay. Results Compared with model group,GLG can markedly reduce MDA level,XOD acitivity and NO contents,in addition,GLG c an effectively increase the ORAC value,GSH content,GSH-PX activity in testis and ovaries. Conclusion Oral treatment of Guangdong Liangcha Granules was found to reduce the status of peroxidation in testis and ovaries,and the improvement may be related to the increase of its free radical scavenging activity and lipid peroxidation.

Effect of Wanglaoji Cool Tea on plasma gluco metabolism and peroxidative state in stress mice / 中成药

AIM:To study the effect of Wanglaoji cool tea(WLJ)(Ilex asprella,Oroxylum indicum,polygnum chinese,Desmadium Styracifolium,Microcos Paniculata,Lophatherum gracile,Lygodium japonicum,Vitex negundo,Helicteres angustifolia,Rosa laevigate) on plasma gluco-metabolism and peroxidative state in stress mice. METHODS: The male BALB/c mice were randomly divided into normal control group,stress control group,positive control group,125 and 500 mg/kg WLJ group,which were administered samples once a day successively for 5 days.After oral administration 2 g/kg glucose into the 20 h stress mice,the elimination rate of plasma glucose,plasma ketone bodies and liver glycogen were determined.The peroxidative state in plasma and antioxidtive capacity of plasma was also measured. RESULTS: As compared with the control groups,WLJ accelerated the basic glucose metabolism of plasma,reduced the plasma ketone body and elevated the liver glycogen synthesis in stress mice.And it also decreased the level of MDA and increased the antioxidant capacity of plasma. CONCLUSION: WLJ improves the glucometabolic dysfunction in stress mice,and the mechanism might be related to the amelioration of peroxidative state in plasma.