Screening and immune infiltration analysis of ferroptosis-related genes in pancreatic cancer with predictions for traditional Chinese medicine treatments

Background:This study aims to explore the involvement of ferroptosis-related genes and pathogenesis in pancreatic cancer and predict potential therapeutic interventions using Traditional Chinese Medicine(TCM).Methods:We utilized gene expression datasets,ferroptosis upregulated genes and applied machine learning algorithms,including LASSO and SVM-RFE,to identify key ferroptosis-related genes in pancreatic cancer.Perform Gene Ontology,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology enrichment analysis,immune infiltration analysis and correlation analysis between immune infiltrating cells and characteristic genes on differentially expressed genes using the R software package.Retrieve potential traditional Chinese medicine for targeted ferroptosis gene therapy for pancreatic cancer through Coremine and Herb databases.Results:Seventeen feature genes were identified,with significant implications for immune cell infiltration in pancreatic cancer.The results of immune cell infiltration analysis showed that B cells naive,B cells memory,T cells regulatory,and M0 macrophages were significantly upregulated in pancreatic cancer patients;Mast cells resting were significantly downregulated.Chinese herbal medicines such as ginkgo,turmeric,ginseng,Codonopsis pilosula,Zedoary turmeric,deer tendons,senna leaves,Guanmu Tong,Huangqi,and Banzhilian are potential drugs for targeted ferroptosis gene therapy for pancreatic cancer.Conclusion:TIMP1 emerged as a key gene,with several TCM herbs predicted to modulate its expression,offering new avenues for treatment.

Effect of cooling rate on solidification microstructure and mechanical properties of TiB2-containing TiAl alloy

Effects of cooling rate and 0.25 at.%TiB2 addition on solidification microstructure and mechanical properties of Ti−48Al−2Cr−2Nb alloys fabricated by the investment casting with different thicknesses were studied.The results show that with the cooling rate increasing from 37 to 2×102 K/s,the solidification path of the studied alloys is unchanged.The grain size of the matrix alloy is refined from 650 to 300μm,while the grain size of Ti−48Al−2Cr−2Nb−TiB2 is reduced from 550 to 80μm.The lamellar spacing of matrix alloy is reduced from 360 to 30 nm with increasing the cooling rate from 37 to 2×102 K/s,while TiB2 addition shows little refinement effect on the lamellar spacing.Ti−48Al−2Cr−2Nb−TiB2 sample under medium cooling rate(69 K/s)exhibits superior microhardness(HV 550)and ultimate tensile strength(570 MPa)among the studied alloys.The refined grain size,lamellar spacing and fine TiB2 particles could account for the favorable mechanical properties of the studied TiB2-containing alloy.The microstructure evolution was discussed in light of cooling rate,constitutional supercooling and borides addition.

Traditional Chinese medicine of Salvia miltiorrhiza Bunge: a review of phytochemistry, pharmacology and pharmacokinetics

Salvia miltiorrhiza Bunge,known as red sage or Danshen,is commonly applied in Chinese herbal therapeutics for various biological effects.In 25-220 C.E.,the earliest Chinese Materia Medica referred to as Shengong’s Classic of Materia Medica(Eastern Han Dynasty of China,200 C.E.)initially documented Salvia miltiorrhiza Bunge.Currently,Salvia miltiorrhiza Bunge is one of the most frequently prescribed traditional Chinese medicines in clinics for antidiabetic,antianxiety,antihypertensive,antidepressant,antilipidemic,antiarrhythmic,and anticancer effects.Undoubtedly,it is best known for improving and promoting blood circulation;thus,its recommendation for use in cardiovascular disorders.Regarding this article,important information was sourced both manually and electronically using patent compendium and databases,including Google Scholar,herbal plant monographs,Hindawi,PubMed,Embase,CNKI,pharmacopoeias,Springer,etc.Well-concise details and discussions on the botany,traditional medicinal uses,chemical constituents-phytochemistry,pharmacokinetics,pharmacology,and toxicology information are presented.In perspective,understanding the comprehensive information of the above-stated fields with regards to Salvia miltiorrhiza Bunge would yield an additional positive knowledge on areas that need urgent attention and identify gaps in research and safety for future consideration.

Compatible stability study of Xing NaoJing injection based on physical-chemical properties analysis

Objective:The clinical treatment of brain diseases is urgent. Xingnaojing (XNJ) injection is often used in combination with other injection drugs. Due to the possible interaction between the injections in vivo, the particle size, osmotic pressure, pH value change and component stability decrease, that is one of the important factors causing various adverse reactions. Based on the above situation, this study investigated the physical properties and chemical composition changes of XNJ injection and its compatibility solvent and 13 kinds of clinical injection, speculated the possible interactions between the drugs in vivo from the perspective of in vitro compatibility stability, find out the safety risks of adverse reactions and provide guidance for the safe and rational use of XNJ injection. Methods:According to the clinical application, XNJ injection was mixed with 13 combination injections based on 250 mL 5% glucose injection, and placed at room temperature for 6 h. Then, the clarity, particle size, pH, osmolality, and the contents of camphor, d-borneol, and muscone of the compatible solutions were detected at 0, 1, 2, 4, and 6 h, respectively. Results:The results showed that the physical-chemical properties of compatibility solution were slightly influenced when XNJ was combined with Alprostadil injection and Danhong injection. The change of particle size and the degradation of muscone content were the main factors affecting the compatibility stability of XNJ injection, indicating that there are some problems in compatibility stability, which may be one of the causes of clinical adverse reactions. Conclusion:This study suggests that XNJ injection in combination with other injections during intravenous administration should be performed cautiously.

Moisture sorption and diffusion determination of Chinese herbal granules:Moisture-resistant effects of fluidized bed granulation with dextrin

Objective: To investigate the effects of fluidized bed granulation with dextrin on moisture sorption and diffusion of Zexie Decoction granules.Methods: The particle characterization was studied by the particle size, scanning electron microscopy(SEM), differential scanning calorimetry(DSC), and Fourier transform infrared(FTIR). The moisture sorption isotherm, equilibrium moisture content(EMC), and moisture diffusion coefficients were determined by using the saturated salt solution method.Results: The particle size increased from 6.04 μm(powder) to 1201.47 μm(granule). The glass transition temperature of dextrin, Zexie Decoction powder, and granule was 107.13 °C, 94.82 °C, and 126.25 °C. As the increase of temperature, the initial rate of moisture sorption become higher. Furthermore, the initial rate of moisture sorption of Zexie Decoction granules was lower than those of powders and dextrin. The EMC and moisture diffusion coefficients were reduced significantly after granulation(P < 0.01). Critical relative humidity and diffusion activation energy of granules were higher than powders.Conclusion: Results suggested that fluidized bed granulation with dextrin could reduce the hygroscopicity of the Zexie Decoction extract powders and inhibited moisture diffusion, which is mainly related to the microstructure reorganization by fluidized bed granulation and anti-plasticizing effects of dextrin.

Cellular model of neuronal atrophy induced by DYNC111 deficiency reveals protective roles of RAS-RAF-MEK signaling

Neuronal atrophy is a common pathological feature occurred in aging and neurodegenerative diseases. A variety of abnormalities including motor protein mal- function and mitochondrial dysfunction contribute to the loss of neuronal architecture; however, less is known about the intracallular signaling pathways that can pro- tect against or delay this pathogenic process. Here, we show that the DYNClll deficiency, a neuron-specific dynein intermediate chain, causes neuronal atrophy in primary hippocampal neurons. With this cellular model, we are able to find that activation of RAS-RAF.MEK signaling protects against neuronal atrophy induced by DYNClll deficiency, which relies on MEK-dependent autophagy in neuron. Moreover, we further reveal that BRAF also protects against neuronal atrophy induced by mitochondrial impairment. These findings demon- strate protective roles of the RAS-RAF-MEK axis against neuronal atrophy, and imply a new therapeutic target for clinical intervention.

Pharmacokinetic study of ginsenoside Re after vaginal administration in rabbits by UPLC-MS/MS determination

Objective: A selective and sensitive ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was employed to study the pharmacokinetics of ginsenoside Re(GRe) in rabbits after vaginal administration of Xiaomi suppository to evaluate the systemic exposure of the suppository for the local treatment.Methods: Chromatographic separation was on an ACQUITY UPLC?BEH C18 column, and acetonitrile-0.1%formic acid was used as mobile phase in gradient elution. The plasma samples were deproteinized by acetonitrile, and the pharmacokinetic parameters were calculated by Winnonlin 6.4.Results: Calibration curve of GRe showed a good linearity over the concentration range from 5 ng/mL to500 ng/mL(r = 0.9999). The low limit of quantification of 5 ng/m L could satisfy the experimental requirement. The intra-day and inter-day precision of GRe at three concentrations were less than 1.96%, and the average recoveries of GRe were more than 64.0%. The pharmacokinetic parameters for vaginal administration were as follows: Tm ax, 0.5 h; C max, 20.88 ng/mL; AUC0-t, 64.71 h · ng/mL and the residence time was3.06 h. By using deconvolution calculation method, the cumulative absorption fraction of GRe was about0.89%.Conclusion: The systemic exposure of GRe was minimal after vaginal administration of Xiaomi suppository.

Trend of non-communicable disease mortality for three common conditions in the elderly population from 2002 to 2010: A population-based study in China

Objective: There is a lack of data focusing on non-communicable disease (NCD) mortality in the Chinese elderly population over the past decade.Methods: Using mortality data from the Chinese Health Statistics, we explored the crude and age-standardized mortality trend of three major NCDs in the Chinese population ≥65 years of age from 2002 to 2010, namely, malignant neoplasms, heart diseases, and cerebrovascular diseases.Subpopulations characterized as rural and urban residence, and by gender and age were examined separately.Results: Mortality increased with age and was higher among males than among females across the three NCDs, with the gender difference being most remarkable for malignant neoplasms and least for heart diseases mortality.Condition-specific crude mortalities increased between 2002 and 2010, overall and in all the pre-specified subpopulations.After age-standardization, rising trends were observed for people ≥65 years old, and condition-specific mortalities generally increased in rural regions and decreased in urban regions, especially for cerebrovascular diseases.Conclusions: There were increasing trends for mortality due to malignant neoplasms, heart diseases, and cerebrovascular diseases in China between 2002 and 2010, which were largely driven by the population aging.Disparities existed by rural and urban residence, gender, and age.Copyright 2015, Chinese Medical Association Production.Production and hosting by Elsevier B.V.on behalf of KeAi Communications Co., Ltd.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).