Studies on pharmacokinetic properties and intestinal absorption mechanism of sanguinarine chloride: in vivo and in situ.

Sanguinarine (SAN) is an alkaloid with multiple biological activities, mainly extracted from Sanguinaria canadensis or Macleaya cordata. The low bioavailability of SAN limits its utilization. At present, the nature and mechanism of SAN intestinal absorption are still unclear. The pharmacokinetics, single-pass intestinal perfusion test (SPIP), and equilibrium solubility test of SAN in rats were studied. The absorption of SAN at 20, 40, and 80 mg/L in different intestinal segments was investigated, and verapamil hydrochloride (P-gp inhibitor), celecoxib (MPR2 inhibitor), and ko143 (BCRP inhibitor) were further used to determine the effect of efflux transporter proteins on SAN absorption. The equilibrium solubility of SAN in three buffer solutions (pH 1.2, 4.5 and 6.8) was investigated. The oral pharmacokinetic results in rats showed that SAN was rapidly absorbed (Tmax=0.5 h), widely distributed (Vz/F = 134 L/kg), rapidly metabolized (CL = 30 L/h/kg), and had bimodal phenomena. SPIP experiments showed that P-gp protein could significantly affect the effective permeability coefficient (Peff) and apparent absorption rate constant (Ka) of SAN. Equilibrium solubility test results show that SAN has the best solubility at pH 4.5. In conclusion, SAN is a substrate of P-gp, and its transport modes include efflux protein transport, passive transport and active transport.

Advancing herbal medicine: enhancing product quality and safety through robust quality control practices.

This manuscript provides an in-depth review of the significance of quality control in herbal medication products, focusing on its role in maintaining efficiency and safety. With a historical foundation in traditional medicine systems, herbal remedies have gained widespread popularity as natural alternatives to conventional treatments. However, the increasing demand for these products necessitates stringent quality control measures to ensure consistency and safety. This comprehensive review explores the importance of quality control methods in monitoring various aspects of herbal product development, manufacturing, and distribution. Emphasizing the need for standardized processes, the manuscript delves into the detection and prevention of contaminants, the authentication of herbal ingredients, and the adherence to regulatory standards. Additionally, it highlights the integration of traditional knowledge and modern scientific approaches in achieving optimal quality control outcomes. By emphasizing the role of quality control in herbal medicine, this manuscript contributes to promoting consumer trust, safeguarding public health, and fostering the responsible use of herbal medication products.

ERBB2 promoter demethylation and immune cell infiltration promote a poor prognosis for cancer patients.

Background: Receptor tyrosine-protein kinase erbB-2 (ERBB2) expression is a critical factor for the prognosis of various cancers. ERBB2 enrichment indicates a poor prognosis in some cancer types but could be a favorable prognostic factor in others. Methods: We analyzed DNA methylation, mRNA, protein, immune cell infiltration, and related signaling pathways using TIMER2.0, GEPIA2, STRING, and UALCAN portal datasets in tumor tissues of diverse cancer types and their matched normal tissues. Results: ERBB2 promoter demethylation increases transcript protein amplification and promotes a poor prognosis for cancer patients. ERBB2 gain-of-function procures immune cell infiltration for tumor growth and drives away T regulatory cells, which suppress or downregulate induction and proliferation of effector T cells. The downstream signaling pathways, such as tumor proliferation, ECM-related genes, and degradation of ECM, are involved in ERBB2 gene demethylation and immune activation in cancer progression. Conclusion: ERBB2 gene demethylation leads to a poor prognosis in cancer patients, which is strongly influenced by the composition and abundance of tumor immune cell infiltration. ERBB2 demethylation could be used in clinical practice to identify immune profiles and direct therapeutic strategies.

Curcumol Suppresses CCF-Mediated Hepatocyte Senescence Through Blocking LC3B-Lamin B1 Interaction in Alcoholic Fatty Liver Disease.

Recent studies indicated that hepatocyte senescence plays an important role in the development of alcoholic fatty liver disease (AFLD), suggesting that inhibition of hepatocyte senescence might be a potential strategy for AFLD treatment. The present study investigated the effect of curcumol, a component from the root of Rhizoma Curcumae, on hepatocyte senescence in AFLD and the underlying mechanisms implicated. The results showed that curcumol was able to reduce lipid deposition and injury in livers of ethanol liquid diet-fed mice and in ethanol-treated LO2 cells. Both in vivo and in vitro studies indicated that supplementation with curcumol effectively alleviated ethanol-induced cellular senescence as manifested by a decrease in senescence-associated ß-galactosidase (SA-ß-gal) activity, a downregulated expression of senescence-related markers p16 and p21, and dysfunction of the telomere and telomerase system. Consistently, treatment with curcumol led to a marked suppression of ethanol-induced formation of cytoplasmic chromatin fragments (CCF) and subsequent activation of cGAS-STING, resulting in a significant reduction in senescence-associated secretory phenotype (SASP)-related inflammatory factors' secretion. Further studies indicated that curcumol's inhibition of CCF formation might be derived from blocking the interaction of LC3B with lamin B1 and maintaining nuclear membrane integrity. Taken together, these results indicated that curcumol was capable of ameliorating AFLD through inhibition of hepatocyte senescence, which might be attributed to its blocking of LC3B and lamin B1 interaction and subsequent inactivation of the CCF-cGAS-STING pathway. These findings suggest a promising use of curcumol in the treatment of AFLD.

Complete Genome Sequence of Lactobacillus acidophilus LA-10A, a Promising Probiotic Strain Isolated from Fermented Mare's Milk.

This report describes the whole-genome sequence of Lactobacillus acidophilus LA-10A, isolated from fermented mare's milk. This strain has been widely consumed due to its excellent performance in the treatment and prevention of Helicobacter pylori infection. The genome sequence of LA-10A provides further molecular information about its features.

Identification of polo-like kinase 1 as a therapeutic target in murine lupus.

INTRODUCTION: The signalling cascades that contribute to lupus pathogenesis are incompletely understood. We address this by using an unbiased activity-based kinome screen of murine lupus. METHODS: An unbiased activity-based kinome screen (ABKS) of 196 kinases was applied to two genetically different murine lupus strains. Systemic and renal lupus were evaluated following in vivo PLK1blockade. The upstream regulators and downstream targets of PLK1 were also interrogated. RESULTS: Multiple signalling cascades were noted to be more active in murine lupus spleens, including PLK1. In vivo administration of a PLK1-specific inhibitor ameliorated splenomegaly, anti-dsDNA antibody production, proteinuria, BUN and renal pathology in MRL.lpr mice (P < 0.05). Serum IL-6, IL-17 and kidney injury molecule 1 (KIM-1) were significantly decreased after PLK1 inhibition. PLK1 inhibition reduced germinal centre and marginal zone B cells in the spleen, but changes in T cells were not significant. In vitro, splenocytes were treated with anti-mouse CD40 Ab or F(ab')2 fragment anti-mouse IgM. After 24-h stimulation, IL-6 secretion was significantly reduced upon PLK1 blockade, whereas IL-10 production was significantly increased. The phosphorylation of mTOR was assessed in splenocyte subsets, which revealed a significant change in myeloid cells. PLK1 blockade reduced phosphorylation associated with mTOR signalling, while Aurora-A emerged as a potential upstream regulator of PLK1. CONCLUSION: The Aurora-A → PLK1 → mTOR signalling axis may be central in lupus pathogenesis, and emerges as a potential therapeutic target.

A Link Between Chemical Structure and Biological Activity in Triterpenoids.

BACKGROUND: Plants that are rich in triterpenoid compounds possess various biological activities and are reported in many scientific works. Triterpenoids, because of their broad sources, wide variety, high medicinal value, and anti-tumor properties, have drawn great attention from scientists. However, the lack of approach to understand the link between their chemical structures and biological activities has limited the fundamental comprehension of these compounds in cancer therapy. OBJECTIVE: The aim of the study is to summarize the list of plants with triterpenoids and their derivatives that are a source of potential novel therapeutic anti-cancer agents by interpreting the network of anti-cancer activity and the structures of triterpenoids and their derivatives. METHODS: This work focuses on analyzing relevant patents and references that detail the structure of triterpenoids and their derivatives for the treatment of tumors. RESULTS: Pentacyclic triterpenoid plays a more important role in improving the autophagic signaling pathways of cancer cells compared to tetracyclic triterpenoid. CONCLUSION: The heterogenous skeleton structure of triterpenoids impairs programmed cell death signaling pathways in various cancers.

Discovery of an EGFR tyrosine kinase inhibitor from Ilex latifolia in breast cancer therapy.

Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as cancer. Some EGFR tyrosine kinase inhibitors have become a new class of targeted therapeutic agents in the last years. We found that 27-O-p-(E)-coumaroyl ursolic acid (27-CAUA) had a strong activity of apoptosis according to preparation by screening for a series of Ilex latifolia products. 27-CAUA inhibited EGFR kinase system to lead to inactivation of PI3K/AKT/mTOR and Ras-Raf-MEK-ERK signal pathways which implicated in the proliferation and survival of tumor cells. These findings suggested that 27-CAUA was an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which could lead to beneficial manifestations in the clinic.

Improving a compact biofilm reactor to realize efficient nitrogen removal performance: step-feed, intermittent aeration, and immobilization technique.

Purifying tank as a compact biofilm reactor has been widely used to remove organic matter in rural sewage, but its potential for nitrogen removal is rare to be discussed. This study developed a lab-scale compact biofilm reactor to realize an efficient nitrogen removal performance by step-feed, intermittent aeration, and immobilization technique. The results show that an efficient simultaneous nitrification and denitrification (SND) process took place by feeding with synthetic wastewater under high C/N ratio of 2 and with real sewage as well, mainly due to the step-feed. The average removal efficiency of total inorganic nitrogen arrived at 72.7 and 63.3% for synthetic wastewater and real sewage, respectively. Besides the step-feed operation, the intermittent aeration was adopted to enhance SND, which allowed hydraulic behavior of compact biofilm reactor following the model of completely stirred tank reactor. The high-throughput sequencing analysis indicates that Sphaerotilus became the dominant genera with relative abundance of 30.29% under high C/N ratio, and the nitrifiers were not greatly inhibited. Moreover, the immobilization technique helped restore microbial activity under low temperature, promoting the satisfactory nitrogen removal performance of recovered microorganism to be rebuilt by feeding nutrient solution. Overall, the long-term SND process and maintaining effective biofilm activity can be established in the compact biofilm reactor through several improving alternatives.

Protein Arrays II: Antigen Arrays.

Antigen arrays are fabricated using various antigens such as DNA, histones, synthetic peptides, recombinant proteins, or cell extracts to detect autoantibodies in autoimmune diseases, alloantibodies in transplantation, drug-induced antibodies or cancer-induced antibodies in blood or cell culture supernatant. In this protocol, we will provide a step-by-step executable procedure to perform antigen arrays, including antigen preparation and printing, blocking, sample loading, array detection, imaging, and data analysis.

Protein Arrays I: Antibody Arrays.

Antibody arrays represent one of the very early protein array systems where antibodies are used to capture and detect target proteins in a high-throughput platform. The development of high-quality antibodies, nanomaterial-based novel detection probes, as well as innovative imaging technologies and computational tools has tremendously improved the sensitivity, specificity, and robustness of antibody arrays during the past decade. In this protocol we will incorporate the most updated innovations and developments of antibody arrays into the step-by-step experimental procedures. This includes antibody printing, sample preparation, array detection, as well as imaging and data analysis. Antibody array could be used for cytokine profiling or mapping of phosphorylation, glycosylation, or other post-translational modifications of target proteins.

Protein Arrays III: Reverse-Phase Protein Arrays.

The reverse-phase protein array (RPPA) is to use highly specific antibodies to interrogate pan or posttranslationally modified protein targets, such as phosphorylated proteins, particularly the proteins involved in cell signaling pathways. In this protocol we will cover the preparation of cell (or tissue) lysates, sample printing, antibody validation, antibody interrogation, signal amplification steps, imaging and data analysis. In this protocol, colorimetric catalyzed signal amplification (CSA) chemistry, fluorescence and near-infrared (NIR) based detection methods will be described.

A Nanoparticle-Decorated Biomolecule-Responsive Polymer Enables Robust Signaling Cascade for Biosensing.

To meet the increasing demands for ultrasensitivity in monitoring trace amounts of low-abundance early biomarkers or environmental toxins, the development of a robust sensing system is urgently needed. Here, a novel signal cascade strategy is reported via an ultrasensitive polymeric sensing system (UPSS) composed of gold nanoparticle (gNP)-decorated polymer, which enables gNP aggregation in polymeric network and electrical conductance change upon specific aptamer-based biomolecular recognition. Ultralow concentrations of thrombin (10-18 m) as well as a low molecular weight anatoxin (165 Da, 10-14 m) are detected selectively and reproducibly. The biomolecular recognition induced polymeric network shrinkage responses as well as dose-dependent responses of the UPSS are validated using in situ real-time atomic-force microscopy, representing the first instance of real-time detection of biomolecular binding-induced polymer shrinkage in soft matter. Furthermore, in situ real-time confocal laser scanning microscopy imaging reveals the dynamic process of gNP aggregation responses upon biomolecular binding.

Urine biomarkers in renal allograft.

There is a high risk for the survival of patients with an end-stage renal disease for kidney transplantation. To avoid rejection by strict medication adherence is of utmost importance to avoid the failure of a kidney transplant. It is imperative to develop non-invasive biomarkers to assess immunity risk, and to ultimately provide guidance for therapeutic decision-making following kidney transplantation. Urine biomarkers may represent the promising non-invasive tools that will help in predicting risk or success rates of kidney transplantations. Furthermore, composite urinary biomarkers or urinary biomarker panel array might be critical in improving the sensitivity and specificity in reflecting various risks of kidney failure during transplantation. This review primarily focuses on the role of such biomarkers in predicting chronic kidney disease (CKD) progression and/or cardiovascular disease (CVD) risk in renal allograft.

Molecular screening of the LPCAT1 gene in patients with retinitis pigmentosa without defined mutations in known retinitis pigmentosa genes.

Retinitis pigmentosa (RP) is an inherited retinopathy, which affects the photoreceptors in the retina. Lysophosphatidylcholine acyltransferase (LPCAT) is a critical phospholipid biosynthesis enzyme, which promotes the conversion of lysophosphatidylcholine into phosphatidylcholine in the remodeling pathway of PC biosynthesis. A previous study reported a homozygous insertion in the LPCAT1 gene in mice exhibiting retinal degeneration (rd11). However, whether genetic mutations in LPCAT1 predispose individuals to RP remains to be elucidated. Therefore, the aim of the present study was to investigate whether LPCAT1 mutations exist in patients with RP. A total of 50 unrelated patients diagnosed with either a sporadic or recessive inheritance pattern of RP were recruited in the present study. All of the patients were comprehensively screened for genes associated with the predisposition of RP, and no pathogenic mutations were identified. Reverse transcription-polymerase chain reaction and Sanger sequencing were performed to investigate the coding regions and exon­intron boundaries of the LPCAT1 gene in the recruited patients. In total, three genetic variations in the coding regions, which lead to amino acid changes, were identified. Although two of these mutations were predicted to be pathogenic, co­segregation analysis in the pedigrees excluded these as disease­causing mutations. In addition, the LPCAT1 gene was screen in a panel of RP patients who exhibited no identifiable mutations in any of the known RP­associated genes. No disease­causing mutations in the LPCAT1 gene were identified, indicating that LPCAT1 either does not confer a genetic predisposition to RP, or that the incidence of mutations in LPCAT1 is particularly rare in patients with RP.

[27-O-(E)-p-coumaric acyl ursolic acid via JNK/SAPK signal pathway regulates apoptosis of human breast cancer MDA-MB-231 cell line].

27-O-(E)-p-coumaric acyl ursolic acid( DY-17) from Ilex latifolia is a compound of the monomer. To investigate the DY-17 inducing apoptosis in the human breast cancer cell line, the MDA-MB-231 cells were used as research object in this experiment. The proliferation activity of the MDA-MB-231 cells stimulated with the different concentrations of DY-17 (20, 40 µmol · L(-1)) was detected at different time( 12, 24, 36, 48, 60,72 h) . We surveyed the DY-17 inducing apoptosis of the MDA-MB-231 cells with the fluorescent staining technology. The rate of MDA-MB-231 cells apoptosis and necrosis was determined by flow cell cytometry (FCC). Moreover, expression of JNK, phosphorylated JNK, Bax, PARP shear and caspase-3 shear related to JNK/SAPK pathways were investigated in every group ( control group, EGF group, EGF + DY-17 40 µmol · L(1) group and EGF + SP600125 group) with Western blot. The MTT results showed that, in the presence of DY-17, the proliferation activity of MDA-MB-231 cells decreased in a dose-dependent and time-dependent manner. The apoptosis and necrosis rates of MDA-MB-231 cells with DY-17(20, 40 µmol · L(-1)) groups was respectively 31.86%, 49.91% by flow cytometry and significantly increased compared with control group under Fluores- cence microscopy. Up-regulation of the JNK phosphorylation protein expression was observed in EGF group compared with control group. In addition, markedly decreased the expression of JNK phosphorylation protein were also surveyed in EGF + DY-17 40 µmol · L(-1) group compared with EGF group. The expression of Bax, shear PARP and shear caspase-3 protein in EGF + DY-17 40 µmol · L(-1) group were significantly increased in comparison with EGF group. The results showed DY-17 induced apoptosis of human breast cancer MDA-MB-231 cell line related to down-regulating JNK/SAPK signal pathways.

[Triterpenoids from Leaves of Ilex latifolia].

OBJECTIVE: To investigate the chemical constituents from the leaves of Ilex latifolia. METHODS: The constituents were iso- lated and purified by various chromatographic techniques. Their structures were identified by UV, IR, MS and NMR spectroscopic analy- sis. RESULTS: Ten compounds were isolated from the leaves of flex latifolia. Their structures were respectively identified as 3ß,13ß-Di- hydroxy-urs-11-en-28-oic acid-13-lactone (1), ß-sitosterol (2) 3-hydroxy-11-oxours-12-ene (3), (20S,24S)-epoxydammarane-3ß,25- diol (4), 25-deuteriostigmasterol (5), α-amyrin (6), foliasalacin A4 (7), 23-hydroxyursolic acid (8), p-coumaric acid (9) and ß-dau- costerol (10). CONCLUSION: Compounds 1,3-5,7 and 9 are isolated from this plant for the first time.

[Effects of watering and nitrogen fertilization on the growth, grain yield, and water- and nitrogen use efficiency of winter wheat].

A field experiment with split-plot design was conducted to study the effects of watering, nitrogen fertilization, and their interactions on the growth, grain yield, and water- and nitrogen use efficiency of winter wheat. Four watering levels (0, 900, 1200, and 1500 m3 x hm(-2)) in main plots and five nitrogen fertilization levels (0, 90, 150, 210, and 270 kg N x hm(-2)) in sub-plots were designed. The results showed that the grain yield, nitrogen absorption, nitrogen use efficiency, and nitrogen productive efficiency of winter wheat increased with increasing level of watering, but the nitrogen use efficiency and nitrogen productive efficiency decreased with increasing nitrogen fertilization level. The grain yield, nitrogen absorption, and nitrogen harvest index were increased with increasing nitrogen fertilization level when the nitrogen application rate was 0-150 kg N x hm(-2), but not further increased significantly when the nitrogen application rate exceeded 150 kg x hm(-2). With the increasing level of watering, the water consumption amount (WCA) and the total water use efficiency increased, while the proportion of precipitation and soil water supply to WCA as well as the irrigation water use efficiency decreased. With the increasing level of nitrogen fertilization, the proportion of precipitation and watering amount to WCA increased, that of soil water supply to WCA decreased, and the total water use efficiency and irrigation water use efficiency decreased after an initial increase, with no significant differences among the treatments of 150, 210, and 270 kg N x hm(-2). It was considered that under our experimental condition, 1500 m3 x hm(-2) of watering amount plus 150 kg x hm(-2) of nitrogen fertilization could be the optimal combination for the high yielding and high efficiency.

Modulation of a super-Gaussian optical needle with high-NA Fresnel zone plate.

A high NA Fresnel zone plate (FZP) is studied using vectorial angular spectrum theory for realizing the sharpest possible super-Gaussian optical needle with purely longitudinal polarization illuminated by a radially polarized vector beam. Strong dispersion of the FZP results in a light field resembling a super-Gaussian optical needle by selecting an optimal FZP structural wavelength relative to the illumination wavelength and inserting a narrow comb window function into the center-shaded FZP. A 25 µm long longitudinally polarized flattop optical needle with a transverse beam width of about 0.366λ is focused at a distance of 222.5 µm away from a binary amplitude 3.46 mm diameter FZP for a 532.4 nm wavelength in free space.

Vectorial design of super-oscillatory lens.

A design and optimization method based on vectorial angular spectrum theory is proposed in this paper for the vectorial design of a super-oscillatory lens (SOL), so that the radially polarized vector beam can be tightly focused. The structure of a SOL is optimized using genetic algorithm and the computational process is accelerated using fast Hankel transform algorithm. The optimized results agree well with what is obtained using the vectorial Rayleigh-Sommerfeld diffraction integral. For an oil immersed SOL, a subwavelength focal spot of about 0.25 illumination wavelength without any significant side lobe can be created at a distance of 184.86 µm away from a large SOL with a diameter of 1mm. The proposed vectorial design method can be used to efficiently design a SOL of arbitrary size illuminated by various vector beams, with the subwavelength hotspot located in a post-evanescent observation plane.