Association of dietary live microbe intake with diabetic kidney disease in patients with type 2 diabetes mellitus in US adults: a cross-sectional study of NHANES 1999-2018.

AIMS: Several studies have reported dietary microorganisms' beneficial effects on human health. We aimed to detect the potential association between dietary live microbe intake and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM) through a cross-sectional analysis of the National Health and Nutrition Examination Survey from 1999 to 2018. METHODS: According to the Sanders classification system of dietary live microbes, the study participants were divided into three groups: low, medium, and high live microbe groups. In patients with T2DM, DKD was assessed by glomerular filtration rate (< 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration algorithm), proteinuria (urinary albumin to creatinine ratio ≥ 30 mg/g), or both. Weighted univariate and multivariate logistic regression and subgroup analyses were conducted to investigate the independent association between dietary live microbe and DKD. RESULTS: The study included 3836 participants, of whom 1467 (38.24%) had DKD for the diagnosis. Our study demonstrated that participants in the high dietary live microbe group were more likely to be older, female, non-Hispanic White, have higher education levels, have a lower prevalence of smoking, have a high poverty-income ratio, have higher energy intake, lower haemoglobin (HbA1c) and serum creatinine levels, and lower risk of progression. After adjustment for covariates, patients in the high dietary live microbe group had a low prevalence of DKD, whereas no significant association with DKD was found between the medium and low dietary live microbe groups. No statistically significant interaction was observed in all subgroup analyses except for HbA1c (p for interaction < 0.05). CONCLUSIONS: Our results indicate that high dietary live microbe intake was associated with a low DKD prevalence.

Association between the composite dietary antioxidant index and chronic kidney disease: evidence from NHANES 2011-2018.

Objectives: There is growing evidence that antioxidant-rich diets protect against chronic kidney disease (CKD). However, the relationship between the Composite Dietary Antioxidant Index (CDAI), an important measure of an antioxidant diet, and CKD has received little attention. Therefore, here we investigated the relationship between the CDAI and CKD through a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data. Methods: The CDAI was calculated based on the intake of six dietary antioxidants. A survey-based multivariate linear regression analysis was performed to analyze the independent relationship between the CDAI and CKD. Weighted multivariate regression and subgroup analyses were conducted to explore the relationship between the CDAI and CKD. Results: A total of 6874 NHANES participants represented 181.9 million non-institutionalized US residents (mean age, 46.43 ± 0.38 years; 49.87% female; 40.62% non-Hispanic white; 20.24% non-Hispanic black; and 13.94% Mexican American). The weighted linear regression model with full adjustment for confounding variables was -0.0155 (-0.0417, 0.0107) for Q2 (P for trend <0.0001), -0.0052 (-0.0346, 0.0242) for Q3 (P for trend <0.0001), and -0.0305 (-0.0491, -0.0120) for Q4 (P for trend = 0.0094) upon comparison with the lowest quartile of the CDAI. None of the interactions in any subgroup analysis were statistically significant except for individuals with a history of diabetes or the aged population (≥60 years) (P for interaction <0.05). Conclusions: The CDAI was positively associated with a lower prevalence of CKD in adults in the United States. Further large-scale prospective studies are required to analyze the role of the CDAI in CKD.

Permeameter and solenoid measurements of Epstein strips of electrical steels.

The dc and ac flux density vs magnetic field B(H) loops of Epstein electrical strips are measured in an IEC type-A permeameter with a high-quality electrical strip wound double yokes of inside length l0 = 0.2 m and inside height h0 = 0.1 m and in a long solenoid. The relevant demagnetizing and eddy-current effects are analyzed, modeled, and discussed. It is concluded that demagnetizing corrected solenoid measurement developed for determining dc B(H) loops of the material cannot be used for the ac case, owing to complicated eddy-current demagnetizing effects. Permeameter-measured ac B(H) loops with H detected by a flat H-coil of length less than l0/2 touching the strip's middle surface may be considered representative of the actual material because H is very uniform along the strip within 3l0/4. Strips with ac B(H) loops thus determined should be used to calibrate the effective magnetic path length lm of Epstein measurements, where a very nonuniform field is applied to the strips.

YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis via aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway.

Objectives: Dimeric pyruvate kinase (PK) M2 (PKM2) plays an important role in promoting the accumulation of hypoxia-inducible factor (HIF)-1α, mediating aberrant glycolysis and inducing fibrosis in diabetic kidney disease (DKD). The aim of this work was to dissect a novel regulatory mechanism of Yin and Yang 1 (YY1) on lncRNA-ARAP1-AS2/ARAP1 to regulate EGFR/PKM2/HIF-1α pathway and glycolysis in DKD. Materials and methods: We used adeno-associated virus (AAV)-ARAP1 shRNA to knocked down ARAP1 in diabetic mice and overexpressed or knocked down YY1, ARAP1-AS2 and ARAP1 expression in human glomerular mesangial cells. Gene levels were assessed by Western blotting, RT-qPCR, immunofluorescence staining and immunohistochemistry. Molecular interactions were determined by RNA pull-down, co-immunoprecipitation, ubiquitination assay and dual-luciferase reporter analysis. Results: YY1, ARAP1-AS2, ARAP1, HIF-1α, glycolysis and fibrosis genes expressions were upregulated and ARAP1 knockdown could inhibit dimeric PKM2 expression and partly restore tetrameric PKM2 formation, while downregulate HIF-1α accumulation and aberrant glycolysis and fibrosis in in-vivo and in-vitro DKD models. ARAP1 knockdown attenuates renal injury and renal dysfunction in diabetic mice. ARAP1 maintains EGFR overactivation in-vivo and in-vitro DKD models. Mechanistically, YY1 transcriptionally upregulates ARAP1-AS2 and indirectly regulates ARAP1 and subsequently promotes EGFR activation, HIF-1α accumulation and aberrant glycolysis and fibrosis. Conclusion: Our results first highlight the role of the novel regulatory mechanism of YY1 on ARAP1-AS2 and ARAP1 in promoting aberrant glycolysis and fibrosis by EGFR/PKM2/HIF-1α pathway in DKD and provide potential therapeutic strategies for DKD treatments.

[Methodology and application of process analytical technology (PAT) for traditional Chinese medicine manufacturing:a review].

Owing to the advancement in pharmaceutical technology, traditional Chinese medicine industry has seen rapid development. Preferring conventional manufacturing mode, pharmaceutical enterprises of traditional Chinese medicine have no effective process detection tools and process control methods. As a result, the quality of the final products mainly depends on testing and the quality is inconsistent in the same batch. Process analytical technology(PAT) for traditional Chinese medicine manufacturing, as one of the key advanced manufacturing techniques, can break through the bottleneck in quality control of medicine manufacturing, thus improving the production efficiency and product quality and reducing the material and energy consumption. It is applicable to the process control and real-time release of advanced manufacturing modes such as intelligent manufacturing and continuous manufacturing. This paper summarized the general idea of PAT for traditional Chinese medicine manufacturing. Through the analysis of the characteristics and status quo of the technology, we summed up the methodology for the continuous application and improvement of PAT during the whole life-cycle of traditional Chinese medicine. The five key procedures(process understanding, process detection, process modeling, process control, and continuous improvement) were summarized, and the application was reviewed. Finally, we proposed suggestions for the technical and regulatory challenges in implementing PAT in traditional Chinese medicine industry. This paper aims to provide a reference for development and application of PAT in advanced manufacturing, intelligent manufacturing, and continuous manufacturing of traditional Chinese medicine industry.

Genetically predicted body fat mass and distribution with diabetic kidney disease: A two-sample Mendelian randomization study.

The aim of this study is to apply a Mendelian randomization (MR) design to investigate the potential causal associations between the body mass index (BMI), body fat mass such as trunk fat mass and waist circumference (WC), and diabetic kidney disease (DKD). A two-sample MR study was conducted to obtain exposure and outcome data from previously published studies. The instrumental variables for BMI, trunk fat mass, and WC were selected from genome-wide association study datasets based on summary-level statistics. The random-effects inverse-variance weighted (IVW) method was used for the main analyses, and the weighted median and MR-Egger approaches were complementary. In total, three MR methods suggested that genetically predicted BMI, trunk fat mass, and WC were positively associated with DKD. Using IVW, we found evidence of causal relationships between BMI [odds ratio (OR) = 1.99; 95% confidence interval (CI), 1.47-2.69; p = 7.89 × 10-6], trunk fat mass (OR = 1.80; 95% CI, 1.28-2.53; p = 6.84 × 10-4), WC (OR = 2.48; 95% CI, 1.40-4.42; p = 1.93 × 10-3), and DKD. MR-Egger and weighted median regression also showed directionally similar estimates. Both funnel plots and MR-Egger intercepts showed no directional pleiotropic effects involving the aforementioned variables and DKD. Our MR analysis supported the causal effect of BMI, trunk fat mass, and WC on DKD. Individuals can substantially reduce DKD risk by reducing body fat mass and modifying their body fat distribution.

[Granulation of Yangxue Qingnao Granules in fluidized bed based on near-infrared spectroscopy].

To realize the real-time monitoring of the production process of Yangxue Qingnao Granules and improve the inter-batch consistency of granule quality in the granulation process, this study established a near-infrared quantitative prediction model of moisture, particle size, bulk density, and angle of repose in the fluidized bed granulation process of Yangxue Qingnao Granules based on near-infrared spectroscopy(NIRS). The near-infrared spectra were collected from 355 samples in 12 batches in the granulation process by integrating the sphere detection module of the near-infrared spectrometer. In combination with the pretreatment methods such as the first derivative, multiplicative scatter correction(MSC), and standard normal variate(SNV), the model was established by partial least squares(PLS) regression. The root mean square error of prediction(RMSEP) of moisture was 0.347 and R_P~2 was 0.935. The RMSEP of the D_(50) particle size model was 38.4 and R_P~2 was 0.980. The RMSEPs of bulk density and angle of repose were 0.018 8 and 0.879, with R_P~2 of 0.085 9 and 0.958. The results showed that the prediction of the PLS quantitative model combined with NIRS was accurate, and this model can be applied to the monitoring of key quality attributes in the fluidized bed granulation of Chinese medicinal granules in the production scale.

Effective magnetic path length in Epstein frame test of electrical steels.

The effective magnetic path length lm for a 25 cm Epstein frame test is studied on the basis of a relevant demagnetizing model and determined by a comparative measurement of dc and ac hysteresis loops at each value of peak flux density Bp, with the field recorded by H-coils placed above the mid-section of the limbs or calculated from the magnetizing current. The obtained Bp and frequency dependences of lm for testing core loss Ps and peak field Hp of an electrical steel are explained in terms of differential susceptibility along the measured loops and demagnetizing and eddy-current effects on local magnetization processes.

[Research on batch-to-batch quality control of compound Danshen extract based on physical characterization and multivariate statistical analysis].

Physical attributes of Chinese herbal extracts are determined by their chemical components, and the physical and chemical attributes jointly affect the preparation process performance and the final product quality. Therefore, in order to improve the quality control of Chinese herbal extracts, we should comprehensively study the batch-to-batch consistency of physical and chemical attributes as well as the correlations between them. This paper first explored the physical attributes affecting the preparation process performance of the compound Danshen extract and developed a method for characterizing the texture attributes. With such main chemical components as water, phenolic acids, saponins, and saccharides and texture, rheology, and other physical attributes taken into consideration, the batch-to-batch quality fluctuation of products from different production lines and time was analyzed by principal components analysis(PCA). Finally, the correlation and partial least squares(PLS) analysis was conducted, and the regression equation was established. The fitting result of the PLS model for dynamic viscosity was satisfying(R~2Y=0.857, Q~2=0.793), suggesting that the chemical components could be adjusted by the component transfer rate in the extraction process, the impurity removal rate in the alcohol precipitation process, and the water retention rate of the concentration process to meet the control of the extract dynamic viscosity. This study clarified the correlations between physical and chemical attributes of the compound Danshen extract and established a method for controlling its physical attributes based on process regulation, which would provide reference for improving the quality control of Chinese herbal extracts.

Predictors of postoperative biochemical remission in acromegaly.

PURPOSE: Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. METHODS: A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3 months in patients after surgery. RESULTS: Of the 546 surgical cases (mean age: 36.8 years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28 µg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28 µg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). CONCLUSIONS: In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

STAT3 Promotes Schistosome-Induced Liver Injury by Inflammation, Oxidative Stress, Proliferation, and Apoptosis Signal Pathway.

Schistosomiasis is a parasitic helminth disease that can cause organ lesions leading to health damage. During a schistosome infection, schistosome eggs can flow into the liver along the portal vein. Numerous inflammatory cells gather around the eggs, causing granulomas and fibrosis in the liver. In this process, many molecules are involved in the initiation and regulation of the fibrous scar formation. However, the precise molecular mechanisms responsible for the progression of granuloma formation and fibrosis initiation caused by schistosome infection have not been extensively studied. In this study, C57BL/6 wild-type mice and Stat3flox/flox Alb-Cre mice were infected with cercariae of Schistosoma japonicum Liver injury, effector molecule levels, and RNA transcriptome resequencing of liver tissue were detected at 4, 5, and 6 weeks postinfection. We investigated the role of STAT3 (signal transducer and activator of transcription 3) in Schistosoma-induced liver injury in mice. After 6 weeks postinfection, there was obvious liver fibrosis. A sustained pathological process (inflammation, oxidative stress, proliferation, and apoptosis) occurred in S. japonicum-induced liver fibrosis initiation. Meanwhile, we observed activation of the STAT3 pathway in hepatic injury during S. japonicum infection by RNA transcriptome resequencing. Liver deficiency of phospho-STAT3 alleviated infection-induced liver dysfunction, hepatic granuloma formation, and fibrosis initiation. It also promoted STAT3-dependent apoptosis and reduced liver inflammation, oxidative stress, and proliferation. Our results suggest that STAT3 signal pathway and its mediating inflammation, oxidative stress, proliferation, and apoptosis are involved in S. japonicum-induced liver injury and may be a new potential guideline for the treatment of schistosomiasis.

[Study of intelligent manufacturing quality digitalization of traditional Chinese medicine and practice on Compound Danshen Dripping Pills].

China healthcare industry has gradually developed the consumer-centric integrated service model. To satisfy consumers' increasing demands on pluralistic, personalized and transparent healthcare services, pharmaceutical manufacturing enterprises must provide high-quality, precise and flexible medicines. This can be achieved by accelerating implementation of intelligent manufacturing, which is the core competitiveness of pharmaceutical manufacturing enterprises. According to the authors' intelligent manufacturing projects in a traditional Chinese medicine(TCM) factory, study and industrial practice on intelligent manufacturing were presented in this paper. First, the quality digitalization-based intelligent manufacturing methodology of TCM was proposed in this paper. The methodology mainly included three digitalized technologies in process and quality design, manufacturing process control and product batch evaluation. Next, the architectural design of intelligent manufacturing systems in one TCM factory was introduced, and the functional modules and data transmission relationships covering seedling, cultivation, herbal slices, preparation, storage and quality management systems were described. Finally, these technologies were fully used, and an integrated quality digitalization system was successfully established in the production workshop of a TCM product Compound Danshen Dripping Pills. The actual operation and application of process analyzers, supervisory control and data acquisition(SCADA), manufacturing execution system(MES), data analysis system, and enterprise resource planning system(ERP) were introduced. This paper provides reference for technical path planning and systematic architecture of TCM intelligent manufacturing.

MicroRNAs and Target Genes in Pituitary Adenomas.

Pituitary adenomas account for the top three primary intracranial tumors in terms of total incidence rates. The clinical symptoms presented by the disease are often characterized by a series of systemic endocrine disorders, severe occupational lesions, and even some malignant features, and therefore early diagnosis and predicting recurrence would be instructive for clinical treatment of pituitary adenomas. An increasing number of specific microRNA (miRNA) expression signatures have been identified in pituitary, and miRNAs are related with the pituitary tumorigenesis, dysfunction, neurodegeneration, and metastatic non-functioning pituitary carcinoma. Here, this paper reviews the effects of aberrant miRNA expression in human pituitary adenomas and summarizes some corresponding target genes and biological significance over the last 7 years (2010-2017).

SUBCLINICAL IMPAIRMENT OF LEFT VENTRICULAR LONGITUDINAL FUNCTION IN PATIENTS WITH PROLACTINOMAS.

OBJECTIVE: Hyperprolactinemia has been associated with endothelial dysfunction and a wide range of cardiovascular risk factors, thus it can potentially lead to cardiac dysfunction. The present study was designed to interrogate our hypothesis that hyperprolactinemia can contribute to preclinical impaired left ventricular function. METHODS: Thirty-one prolactinoma patients and 60 healthy volunteers were prospectively recruited. Left ventricular function was evaluated using conventional two dimensions and M-mode echocardiography, as well as Doppler tissue imaging (DTI). RESULTS: The Tei index (0.45 ± 0.06 vs. 0.41 ± 0.03, P = .005) and ratio of transmitral and myocardial early diastolic velocities (E/Em; 6.30 ± 1.45 vs. 5.64 ± 0.69, P = .045) were significantly higher, and septal systolic velocity (Sm; 9.88 ± 1.45 vs. 11.58 ± 1.28 cm/s, P<.001) was significantly lower in prolactinoma patients. Furthermore, significant motional abnormalities were detected in regional segments of prolactinoma patients. Pearson's correlation analysis revealed that prolactin level was inversely associated with Sm (r = -0.373, P = .009) and late diastolic phase (Am; r = -0.293, P = .043). Moreover, inverse correlations between prolactin and partial left ventricular segment wall motion were found, including the basal (r = -0.363, P = .014), middle (r = -0.418, P = .004), and apical segment (r = -0.574, P<.001) of the posterior ventricular septum. Multivariate linear regression analysis revealed that prolactin (ß = -0.28, 95% confidence interval -0.011 to 0, P = .035), as a single factor, can significantly predict decreased Sm, independent of traditional vascular risk factors. CONCLUSION: Our results suggest that subclinical cardiac dysfunction occurs in untreated prolactinoma patients and is characterized by impaired systolic and diastolic function of the left ventricle, as well as regional segment motional abnormality. ABBREVIATIONS: A = transmitral late diastolic velocity Am = late diastolic phase Apo = apolipoprotein DTI = Doppler tissue imaging E = transmitral early diastolic velocity Em = myocardial early diastolic velocity FMD = flow-mediated dilation HOMA-IR = homeostasis model assessment of insulin resistance hsCRP = high-sensitivity C-reactive protein IMT = intima media thickness LDL-C = low-density lipoprotein cholesterol LV = left ventricular PPCM = postpartum cardiomyopathy Sm = septal systolic velocity.

Taurine drinking ameliorates hepatic granuloma and fibrosis in mice infected with Schistosoma japonicum.

In schistosomiasis, egg-induced hepatic granuloma formation is a cytokine-mediated, predominantly CD4(+) Th2 immune response that can give rise to hepatic fibrosis. Hepatic fibrosis is the main cause of increased morbidity and mortality in humans with schistosome infection. Taurine has various physiological functions and hepatoprotective properties as well as anti-inflammatory and immunomodulatory activity. However, little is known about the role of taurine in schistosome egg-induced granuloma formation and fibrosis. We aimed to evaluate the therapeutic potential of taurine as preventative treatment for Schistosoma japonicum infection. Mice infected with S. japonicum cercariae were supplied with taurine drinking water (1% w/v) for 4 weeks starting at 4 weeks post-infection. Taurine supplementation significantly improved the liver pathologic findings, reduced the serum levels of aminotransferases and area of hepatic granuloma, and prevented fibrosis progression. In addition, taurine decreased the expression of the granulomatous and fibrogenic mediators transforming growth factor ß1, tumor necrosis factor α, monocyte chemotactic protein 1α and macrophage inflammatory protein 1α as well as the endoplasmic reticulum stress marker glucose-regulated protein 78. Thus, taurine can significantly attenuate S. japonicum egg-induced hepatic granuloma and fibrosis, which may depend in part on the downregulation of some relevant cytokine/chemokines and reducing the endoplasmic reticulum stress response.

Expression profiling of O(6) methylguanine-DNA-methyl transferase in prolactinomas: a correlative study of promoter methylation and pathological features in 136 cases.

BACKGROUND: Low-level expression of O(6) methylguanine-DNA-methyl transferase (MGMT) prolactinomas has been noted previously in case reports, although what modulates MGMT expression remains unclear. This study therefore aimed to delineate the factors regulating MGMT expression in prolactinomas. METHODS: We retrospectively reviewed 136 prolactinoma patients who were treated in our center between January 2000 and September 2013. Expression of MGMT, Ki-67, and p53 protein were examined by immunohistochemical staining, and MGMT promoter methylation evaluated with methylation-specific PCR. RESULTS: MGMT immunopositivity was <25 % in 106/136 tumor specimens (77.94 %). MGMT immunoexpression was positively correlated with age (r = 0.251, p = 0.003), but inversely correlated with p53 staining (r = -0.153, p = 0.021). Moreover, reduced MGMT expression was more frequent in atypical prolactinomas (p = 0.044). Methylated MGMT promoter was confirmed in 10/46 specimens (21.7 %), all of which had low level or absent MGMT staining. Both p53 protein (r = -0.33, p = 0.025) and promoter methylation (r = -0.331, p = 0.025) were negatively associated with MGMT expression. Multivariate logistic analysis indicated that age (odds ratio [OR] = 1.127. 95 % confidence interval [CI] 1.027-1.236, p = 0.012) and p53 (OR = 0.116. 95 % CI 0.018-0.761, p = 0.025) staining were independent determents of MGMT expression. CONCLUSIONS: The majority of prolactinomas, especially atypical prolactinomas, showed low-level or no MGMT immunoexpression, providing a rationale for the utility of temozolomide as an alternative to managing prolactinomas. In summary, epigenetic and transcriptional regulation are involved in silencing MGMT expression.

The marine metabolite SZ-685C induces apoptosis in primary human nonfunctioning pituitary adenoma cells by inhibition of the Akt pathway in vitro.

Nonfunctioning pituitary adenoma (NFPA) is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403) which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay) to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs) and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI) double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI) apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN) were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.

Salvianolic acids T and U: a pair of atropisomeric trimeric caffeic acids derivatives from root of Salvia miltiorrhiza.

Two new trimeric caffeic acids, named salvianolic acids T and U (1 and 2), were isolated from the underground part of Salvia miltiorrhiza. Their structures, consisting of three caffeic acid units, were determined based on extensive 1D- and 2D-spectroscopic analyses and electronic circular dichroism (ECD) calculations.

Clinical applications of somatostatin analogs for growth hormone-secreting pituitary adenomas.

Excessive growth hormone (GH) is usually secreted by GH-secreting pituitary adenomas and causes gigantism in juveniles or acromegaly in adults. The clinical complications involving cardiovascular, respiratory, and metabolic systems lead to elevated morbidity in acromegaly. Control of serum GH and insulin-like growth factor (IGF) 1 hypersecretion by surgery or pharmacotherapy can decrease morbidity. Current pharmacotherapy includes somatostatin analogs (SAs) and GH receptor antagonist; the former consists of lanreotide Autogel (ATG) and octreotide long-acting release (LAR), and the latter refers to pegvisomant. As primary medical therapy, lanreotide ATG and octreotide LAR can be supplied in a long-lasting formulation to achieve biochemical control of GH and IGF-1 by subcutaneous injection every 4-6 weeks. Lanreotide ATG and octreotide LAR provide an effective medical treatment, whether as a primary or secondary therapy, for the treatment of GH-secreting pituitary adenoma; however, to maximize benefits with the least cost, several points should be emphasized before the application of SAs. A comprehensive assessment, especially of the observation of clinical predictors and preselection of SA treatment, should be completed in advance. A treatment process lasting at least 3 months should be implemented to achieve a long-term stable blood concentration. More satisfactory surgical outcomes for noninvasive macroadenomas treated with presurgical SA may be achieved, although controversy of such adjuvant therapy exists. Combination of SA and pegvisomant or cabergoline shows advantages in some specific cases. Thus, an individual treatment program should be established for each patient under a full evaluation of the risks and benefits.