Research Progress on Sesquiterpenoids of Curcumae Rhizoma and Their Pharmacological Effects.

Curcumae Rhizoma, a traditional Chinese medicine with a wide range of pharmacological activities, is obtained from the dried rhizomes of Curcuma phaeocaulis VaL., Curcuma kwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling. Sesquiterpenoids and curcuminoids are found to be the main constituents of Curcumae Rhizoma. Sesquiterpenoids are composed of three isoprene units and are susceptible to complex transformations, such as cyclization, rearrangement, and oxidation. They are the most structurally diverse class of plant-based natural products with a wide range of biological activities and are widely found in nature. In recent years, scholars have conducted abundant studies on the structures and pharmacological properties of components of Curcumae Rhizoma. This article elucidates the chemical structures, medicinal properties, and biological properties of the sesquiterpenoids (a total of 274 compounds) isolated from Curcumae Rhizoma. We summarized extraction and isolation methods for sesquiterpenoids, established a chemical component library of sesquiterpenoids in Curcumae Rhizoma, and analyzed structural variances among sesquiterpenoids sourced from Curcumae Rhizoma of diverse botanical origins. Furthermore, our investigation reveals a diverse array of sesquiterpenoid types, encompassing guaiane-type, germacrane-type, eudesmane-type, elemane-type, cadinane-type, carane-type, bisabolane-type, humulane-type, and other types, emphasizing the relationship between structural diversity and activity. We hope to provide a valuable reference for further research and exploitation and pave the way for the development of new drugs derived from medicinal plants.

Persistent Viral Presence Determines the Clinical Course of the Disease in COVID-19.

BACKGROUND: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome. OBJECTIVE: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles. METHODS: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery. RESULTS: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established. CONCLUSIONS: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19.

Mink Aleutian disease seroprevalence in China during 1981-2017: A systematic review and meta-analysis.

Mink Aleutian disease (AMD) is the first of the three major diseases of fur animals. It is a common immunosuppressive disease in mink farms worldwide, which seriously endangers the development of the mink farming industry. Strengthening the understanding of the positive serum rate and spatial distribution of AMD is of great significance for the prevention and control of disease caused by the Aleutian virus. Therefore, we conducted a systematic review and meta-analysis to assess the seroprevalence of AMD in China. We extracted 45 studies related to the seroprevalence of Chinese AMD, with samples taken between 1981 and 2017. Our systematic review and meta-analysis results show that, during the selected period, the overall positive rate of AMD in China was 55.3% (95% CI 48.5-62.0). The results from subgroups analysis of the potential risk factors showed that the seroprevalence rate of AMD in China in the past 36 years rose from 48% (95% CI 37.0-60.5) in 1981-2009 to 61.4% (95% CI 43.6-79.3) in 2010-2017. The date of the spatial difference in AMD seroprevalence indicated that AMD seroprevalence was unevenly distributed in different regions: the number of mink in eastern China and northeastern China was relatively high, and the seroprevalence rates were 57.9%, (95% CI 46.2-69.7) and 61.3% (95% CI 53.1-69.5), respectively. Central China had the highest seroprevalence rate of AMD at 69.8% (95% CI 64.4-75.2). At the provincial level, the AMD seroprevalence rate in Jiangsu was as high as 96% (95% CI 94.1-97.8), and the AMD seroprevalence rate in Shaanxi was the lowest at 22.1% (95% CI 20.3-23.9). This suggested that the AMD seroprevalence rate in China was unevenly distributed. In other subgroups, the positive rate of AMD in adult mink was higher than in juvenile mink. This implied that the high prevalence of AMD in China was caused by multiple factors. The meta-regression results indicated that the detection method subgroup (P = 0.008) may be the source of heterogeneity. Our data system evaluated the prevalence of Aleutian disease in China in the last 37 years and a preliminary discussion on the risk factors of AMD. It may help prevent and control AMD in China. It is recommended to conduct further epidemiological testing and develop a comprehensive testing plan to determine the risk factors associated with Aleutian disease and improve the Aleutian disease control strategy.

Tip Crack Imaging on Transparent Materials by Digital Holographic Microscopy.

With this study, we propose a method to image the tip crack on transparent materials by using digital holographic microscopy. More specifically, an optical system based on Mach-Zehnder interference along with an inverted microscopy (Olympus CKX53) was used to image the tip crack of Dammar Varnish transparent material under thermal excitation. A series of holograms were captured and reconstructed for the observation of the changes of the tip crack. The reconstructed holograms were also compared temporally to compute the temporal changes, showing the crack propagation phenomena. Results show that the Dammar Varnish is sensitive to the ambient temperature. Our research demonstrates that digital holographic microscopy is a promising technique for the detection of the fine tip crack and propagation in transparent materials.

Prevalence and Risk Factors of Brucellosis, Chlamydiosis, and Bluetongue Among Sika Deer in Jilin Province in China.

Brucellosis and chlamydiosis are important zoonotic diseases and bluetongue virus (BTV) is an arthropod-borne viral disease of ruminants. They are widely distributed around the world, cause large economic losses, and significant harmful effects on humans. However, epidemiological information relating to transmission from commercial sika deer in China is limited. Therefore, from 2016 to 2017, 458 sika deer blood samples were collected from three cities in Jilin Province in China. The Brucella antigen and specific antibodies to Chlamydia and BTV were examined using RT-PCR, indirect hemagglutination assay, and ELISA, respectively. The prevalence of Brucella was found to be 12.9% (59/458) and the seroprevalence of Chlamydia and BTV was 14.4% (66/458) and 17.0% (78/458), respectively. Seasonality was considered a risk factor for the presence of Brucella or BTV in sika deer and the region was considered a risk factor for Chlamydia infection. These data provides reference values for both further research and disease control.

Effect of coronary artery revascularization on in-hospital outcomes and long-term prognoses in acute myocardial infarction patients with prior ischemic stroke.

OBJECTIVE: To investigate whether coronary artery revascularization therapies (CART), including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG), can improve the in-hospital and long-term outcomes for acute myocardial infarction (AMI) patients with prior ischemic stroke (IS). METHODS: A total of 387 AMI patients with prior IS were enrolled consecutively from January 15, 2005 to December 24, 2011 in this cohort study. All patients were categorized into the CART group (n = 204) or the conservative medications (CM) group (n = 183). In-hospital cardiocerebral events and long-term mortality of the two groups after an average follow-up of 36 months were recorded by Kaplan-Meier survival curves and compared by Logistic regression and the Cox regression model. RESULTS: The CART patients were younger (66.5 ± 9.7 years vs. 71.7 ± 9.7 years, P < 0.01), had less non-ST segment elevation myocardial infarction (11.8% vs. 20.8%, P = 0.016) and more multiple-vascular coronary lesions (50% vs. 69.4%, P = 0.031). The hospitalization incidence of cardiocerebral events in the CART group was 9.3% while 26.2% in the CM group (P < 0.01). CART significantly reduced the risk of in-hospital cardiocerebral events by 65% [adjusted odds ratio (OR) = 0.35, 95% CI: 0.13-0.92]. By the end of follow-up, 57 cases (41.6%) died in CM group (n = 137) and 24 cases (12.2%) died in CART group (n = 197). Cox regression indicated that CART decreased the long-term mortality by 72% [adjusted hazard ratio (HR) = 0.28, 95% CI: 0.06-0.46], while categorical analysis indicated no significant difference between PCI and CABG. CONCLUSIONS: CART has a significant effect on improving the in-hospital and long-term prognoses for AMI patients with prior IS.

Impact of Mean Platelet Volume on Long-Term Mortality in Chinese Patients with ST-Elevation Myocardial Infarction.

We investigated the association between mean platelet volume (MPV) and risk of all-cause mortality in Chinese patients with ST-Elevation Myocardial Infarction (STEMI). We enrolled 1836 patients with STEMI in Xuanwu Hospital from January 2008 to December 2013. Based on MPV, patients were categorized into the following groups: < 9.5 fL (n = 85), 9.5-11.0 fL (n = 776), 11.1-12.5 fL (n = 811) and >12.5 fL (n = 164), respectively. Mean duration of follow-up was 56.9 months, and 197 patients (10.7%) died during follow-up. All-cause mortality rates were compared between groups. The lowest mortality occurred in patients with MPV between 9.5-11.0 fL, with a multivariable-adjusted hazard ratio (HR) of 1.15(95%CI 0.62-1.50), 1.38(95%CI 1.20-1.68), and 1.72(95%CI 1.41-1.96) in patients with MPV of <.5, 11.1-12.5 and >12.5 fL, respectively. Therefore, increased MPV was associated with all-cause mortality in Chinese patients with STEMI. MPV might be useful as a marker for risk stratification in Chinese patients with STEMI.

Protective effect of Bu-7, a flavonoid extracted from Clausena lansium, against rotenone injury in PC12 cells.

AIM: To investigate the protective effect and underlying mechanisms of Bu-7, a flavonoid isolated from the leaves of Clausena lansium, against rotenone-induced injury in PC12 cells. METHODS: The cell viability was evaluated using MTT assay. The cell apoptosis rate was analyzed using flow cytometry. JC-1 staining was used to detect the mitochondrial membrane potential (MMP). Western blotting analysis was used to determine the phosphorylation of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), tumor protein 53 (p53), Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and caspase 3. RESULTS: Treatment of PC12 cells with rotenone (1-20 µmol/L) significantly reduced the cell viability in a concentration-dependent manner. Pretreatment with Bu-7 (0.1 and 10 µmol/L) prevented PC12 cells from rotenone injury, whereas Bu-7 (1 µmol/L) had no significant effect. Pretreatment with Bu-7 (0.1 and 10 µmol/L) decreased rotenone-induced apoptosis, attenuated rotenone-induced mitochondrial potential reduction and suppressed rotenone-induced protein phosphorylation and expression, whereas Bu-7 (1 µmol/L) did not cause similar effects. Bu-7 showed inverted bell-shaped dose-response relationship in all the effects. CONCLUSION: Bu-7 protects PC12 cells against rotenone injury, which may be attributed to MAP kinase cascade (JNK and p38) signaling pathway. Thus, Bu-7 may be a potential bioactive compound for the treatment of Parkinson's disease.

Effect of all-trans retinoic acid combined with trichostatin A on the nude mice bearing human follicular thyroid carcinoma / 中华核医学杂志

ObjectiveTo study the changes of iodine uptake of the follicular thyroid carcinoma cell line (FTC-133) and nude mice bearing human follicular thyroid carcinoma after the induction with alltrans retinoic acid (ATRA),trichostatin A (TSA) or ATRA combined with TSA.MethodsAfter the induction with ATRA,TSA,or ATRA combined with TSA in different concentrations for 96 h,the iodine uptake of FTC-133 cells was observed.The concentrations for different groups were as follows:ATRA 1.0 ×10-6 mol/L(Alow group),ATRA 1.0 × 10-4 mol/L(Ahigh group),TSA 1.65 ×10-7 mol/L(T group),Alow +T group,Ahigh +T group and ethanol (control group).Cell quantities and morphology were observed by HE staining.FTC-133 cells were subcutaneously injected into nude mice.Twelve nude mice were randomly divided into 4 groups after tumor formation:ATRA group (2 mg/kg,intragastric administration),TSA group (10 mg/kg,intraperitoneal injection),combined therapy group (ATRA + TSA,the same doses as above) and saline control group (10 ml/kg,intragastric and intraperitoneal administration,respectively).Drugs were administered to the tumor-bearing mice according to the mouse body mass daily.At the 22nd day,the tumor-bearing mice were injected with 37 MBq 131I intraperitoneally.The biodistribution of 131I and gamma imaging were performed at 4,6,12 and 24 h after the injection respectively.Histopathological examinations of the tumor samples were taken after imaging completion.The results were analyzed by analysis of variance (ANOVA) with SPSS 13.0.ResultsThe cellular iodine uptake were (23 885 ± 616.0 ) and ( 13 849 ±728.2) counts · min-1 · 10-6 cells in the Alow + T group and Ahigh + T group respectively,and the data were (985 ± 84.2) - ( 17 600 ± 782.7 ) counts · min-1 · 10-6 in the other groups ( F =600.879,P ＜0.001 ).The ％ ID/g of tumor at 6 h was 6.17 ±0.46 in the combined group and it increased to 9.34 ±0.61 at 12 h and 11.19 ± 0.98 at 24 h.The ％ ID/g of tumor in the other groups were from ( 1.97 ± 0.34)to (5.14 ± 0.65 ).The tumor qualities of the 4 groups were significantly different ( F =3.723,P ＜ 0.05 ).ConclusionThe iodine uptake of the tumor could be enhanced in the tumor-bearing mice administered with ATRA combined with TSA,a potential way for treating follicular thyroid carcinoma.

InCl(3)-catalyzed asymmetric aza-Friedel-Crafts reaction of indoles with imines generated from O-pivaloylated beta-D-galactosylamine.

The highly diastereoselective InCl(3)-catalyzed aza-Friedel-Crafts reaction of substituted indoles with aldimines generated from Kunz's amine was studied. The reaction afforded the desired product in good to high yields with up to >19:1 diastereoselective ratios. The O-pivaloylated beta-D-galactosyl moiety could not be cleaved under the traditional acidic conditions. It was removed successfully after unmasking of the O-pivaloyl groups using MeOH/NaOMe and treatment with HOAc/H(2)O subsequently, to yield the 3-indolyl aryl methanamine derivatives in high optical purity.

Combined effects of all-trans-retinoic acid and trichostatin A on the induction of differentiation of thyroid carcinoma cells / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The effectiveness rate of all-trans-retinoic acid (RA) is only about 30% in the clinical application of inducing thyroid carcinoma differentiation. In addition, there are severe toxic side effects, which limit its clinical application. Phase I-III clinical studies have been conducted on the combined application of two or more kinds of inductors in tumors. Nevertheless, the combination of RA with histone deacetylase inhibitors is rarely reported. This article studied the effects of differentiation for papillary thyroid carcinoma and follicular thyroid carcinoma cell lines induced by RA combined with trichostatin A (TSA), enhancing the effect of induction, while reducing the toxic side effects of a single drug, to provide a theoretical basis for preclinical trials.</p><p><b>METHODS</b>After incubation with RA combined with TSA, K1 and FTC-133 were grouped into Group 1 (RA 10(-4) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 2 (RA 1 x 10(-4) mol/L plus TSA 3.31 x 10(-7) mol/L), Group 3 (RA 10(-5) mol/L plus TSA 1.65 x 10(-7) mol/L), Group 4 (RA 1 x10(-5) mol/L plus TSA 3.31 x 10(-7) mol/L) by four varied concentrations and three time points (12 h, 24 h, and 48 h). The cell proliferation, conformation, toxic effect, and induced differentiation on K1 and FTC-133 cell lines were studied microscopically with hematoxylin-eosin (HE) to observe cell quantity and morphology, methyl-thiazolyl-tetrazolium (MTT) to calculate cell survival rates, and electrochemiluminescence analysis measuring in vitro thyroglobulin (Tg) levels.</p><p><b>RESULTS</b>The research showed that K1 and FTC-133 cells had cell spacing increases, with an outer edge of smooth, nuclear chromatin condensation after RA combined TSA. Survival rate were assessed by an analysis of variance (ANOVA) by concentration and time point, F values of K1 and FTC-133 were 23.52 and 170.14, and 57.09 and 224.35, respectively. There were significant differences for both cells (P < 0.01). The SNK analysis indicated that survival rates were in the order of Group 2 < Group 1 < Group 4 < Group 3. Tg was also assessed by ANOVA, F values of K1 were 69.63 and 101.07, and F values of FTC-133 were 79.77 and 81.72 (P < 0.01). Group 1 was compared with Group 3 of K1 and FTC-133 by the least significant difference (LSD) method, and there was no statistical difference between the two group (P = 0.06, 0.2, respectively; P > 0.05), yet a significant difference was seen between the other Groups.</p><p><b>CONCLUSIONS</b>Lower concentrations of RA combined with lower concentrations of TSA have both inhibited cell proliferation, decreased toxicity of the drugs, and increased the effect of K1 and FTC-133 cell differentiation. The mechanism of action may be that TSA has pretranscription DNA regulation and that RA has posttranscriptional signal regulation to enhance the effects of inhibited proliferation and differentiation of cells by transcription systems.</p>

Polygalasaponin XXXII from Polygala tenuifolia root improves hippocampal-dependent learning and memory.

AIM: The aim of this study was to investigate the cognition-enhancing activity and underlying mechanisms of a triterpenoid saponin (polygalasaponin XXXII, PGS32) isolated from the roots of Polygala tenuifolia Willd. METHODS: The Morris water maze was used to evaluate the spatial learning and memory of mice. To detect the basic properties of synaptic transmission and long-term potentiation (LTP) in the dentate gyrus of rats, electrophysiological recordings were made of evoked potentials. Western blotting analysis and immunofluorescence assays were used to determine the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), synapsin I and the expression of brain derived neurotrophic factor (BDNF). RESULTS: When administered at 0.125, 0.5, or 2 mg/kg, PGS32 could significantly prevent scopolamine-induced cognitive impairments in mice. Intracerebroventricular (icv) administration of PGS32 greatly enhanced basic synaptic transmission in the dentate gyrus of rats and induced LTP. In primary hippocampal neurons, as well as in the hippocampus of maze-trained mice, PGS32 activated the mitogen-activated protein (MAP) kinase cascade by promoting phosphorylation of ERK, CREB and synapsin I. The expression of BDNF was also greatly enhanced in the hippocampus. CONCLUSION: Our findings suggest that PGS32 can improve hippocampus-dependent learning and memory, possibly through improvement of synaptic transmission, activation of the MAP kinase cascade and enhancement of the level of BDNF. Therefore, PGS32 shows promise as a potential cognition-enhancing therapeutic drug.

PEG-conjugated PAMAM dendrimers mediate efficient intramuscular gene expression.

Generations 5 and 6 (G5 and G6) poly(amidoamine) (PAMAM) dendrimers have been shown to be highly efficient nonviral carriers in in vitro gene delivery. However, their high toxicity and unsatisfied in vivo efficacy limit their applications. In this study, to improve their characteristics as gene delivery carriers, polyethylene glycol (PEG, molecular weight 5,000) was conjugated to G5 and G6 PAMAM dendrimers (PEG-PAMAM) at three different molar ratios of 4%, 8%, and 15% (PEG to surface amine per PAMAM dendrimer molecular). Compared with unconjugated PAMAM dendrimers, PEG conjugation significantly decreased the in vitro and in vivo cytotoxicities and hemolysis of G5 and G6 dendrimers, especially at higher PEG molar ratios. Among all of the PEG-PAMAM dendrimers, 8% PEG-conjugated G5 and G6 dendrimers (G5-8% PEG, G6-8% PEG) resulted in the most efficient muscular gene expression when polyplexes were injected intramuscularly to the quadriceps of neonatal mice. Consistent with the in vivo results, these two 8% PEG-conjugated PAMAM dendrimers could also mediate the highest in vitro transfection in 293A cells. Therefore, G5-8% PEG and G6-8% PEG possess a great potential for gene delivery both in vivo and in vitro.