Advancements of Macrophages Involvement in Pathological Progression of Colitis-Associated Colorectal Cancer and Associated Pharmacological Interventions.

Intestinal macrophages play crucial roles in both intestinal inflammation and immune homeostasis. They can adopt two distinct phenotypes, primarily determined by environmental cues. These phenotypes encompass the classically activated pro-inflammatory M1 phenotype, as well as the alternatively activated anti-inflammatory M2 phenotype. In regular conditions, intestinal macrophages serve to shield the gut from inflammatory harm. However, when a combination of genetic and environmental elements influences the polarization of these macrophages, it can result in an M1/M2 macrophage activation imbalance, subsequently leading to a loss of control over intestinal inflammation. This shift transforms normal inflammatory responses into pathological damage within the intestines. In patients with ulcerative colitis-associated colorectal cancer (UC-CRC), disorders related to intestinal inflammation are closely correlated with an imbalance in the polarization of intestinal M1/M2 macrophages. Therefore, reinstating the equilibrium in M1/M2 macrophage polarization could potentially serve as an effective approach to the prevention and treatment of UC-CRC. This paper aims to scrutinize the clinical evidence regarding Chinese medicine (CM) in the treatment of UC-CRC, the pivotal role of macrophage polarization in UC-CRC pathogenesis, and the potential mechanisms through which CM regulates macrophage polarization to address UC-CRC. Our objective is to offer fresh perspectives for clinical application, fundamental research, and pharmaceutical advancement in UC-CRC.

Efficacy and safety of Fuzheng Huayu tablet on persistent advanced liver fibrosis following 2 years entecavir treatment: A single arm clinical objective performance criteria trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Antiviral therapy can alleviate liver fibrosis in chronic hepatitis B, but it has a limited effect on advanced liver fibrosis/cirrhosis. Traditional Chinese medicine (TCM), particularly FuZheng HuaYu (FZHY) tablet, appears to have an antifibrotic effect, but its improving resolution of hepatitis b virus (HBV) -associated advanced fibrosis and experienced anti-viral treatment has not been investigated. AIM OF THE STUDY: To observe the safety and efficacy of adjunctive FZHY on the HBV-associated cirrhosis patients who received 2 years of entecavir but still with advanced fibrosis. METHODS: An open-label, multicentre, single arm trial. 251 patients were included and treated with TCM consisted of FZHY tablets 1.6 g and granules, three times a day in addition to entecavir 0.5 mg daily for an additional 48 weeks. Primary outcome was regression of fibrosis (the proportion of patients with a 1-point decrease in the Ishak liver fibrosis score from baseline to week 48). RESULTS: Fibrosis regression occurred in 94 of 184 patients with paired liver biopsy (51.09%, 95% CI: 43.9～58.0). In 132 compensated cirrhosis patients (Ishak score ≥5), 56.06% (74/132, 95% CI: 47.5～64.2) showed fibrosis regression and reached the goal of 54% (15% more than entecavir mono-therapy). 10 patients occurred adverse reaction, most of them were mild, and all recovered or achieved remission. CONCLUSIONS: The combination therapy of FZHY, TCM granules and ETV could regress the liver fibrosis in the patients with HBV cirrhosis, who experienced 2 years of ETV treatment, and it is safe and well tolerated.

Arm locking using laser frequency comb.

The space-borne gravitational wave (GW) detectors, e.g., LISA, TaiJi, and TianQin, will open the window in the low-frequency regime (0.1 mHz to 1 Hz) to study the highly energetic cosmic events, such as coalescences and mergers of binary black holes and neutron stars. For the sake of successful observatory of GWs, the required strain sensitivity of the detector is approximately 10-21/Hz1/2 in the science band, 7 orders of magnitude better than the state of the art of the ultra-stable laser. Arm locking is therefore proposed to reduce the laser phase noise by a few orders of magnitude to relax the burden of time delay interferometry. During the past two decades, various schemes have been demonstrated by using single or dual arms between the spacecraft, with consideration of the gain, the nulls in the science band, and the frequency pulling characteristics, etc. In this work, we describe an updated version of single arm locking, and the noise amplification due to the nulls can be flexibly restricted with the help of optical frequency comb. We show that the laser phase noise can be divided by a specific factor with optical frequency comb as the bridge. The analytical results indicate that, the peaks in the science band have been greatly reduced. The performance of the noise suppression shows that the total noise after arm locking can well satisfy the requirement of time delay interferometry, even with the free-running laser source. When the laser source is pre-stabilized to a Fabry-Perot cavity or a Mach-Zehnder interferometer, the noise can reach the floor determined by the clock noise, the spacecraft motion, and the shot noise. We also estimate the frequency pulling characteristics of the updated single arm locking, and the results suggest that the pulling rate can be tolerated, without the risk of mode hopping. Arm locking will be a valuable solution for the noise reduction in the space-borne GW detectors. We demonstrate that, with the precise control of the returned laser phase noise, the noise amplification in the science band can be efficiently suppressed based on the updated single arm locking. Not only does our method allow the suppression of the peaks, the high gain, and low pulling rate, it can also serve for full year, without the potential risk of locking failure due to the arm length mismatch. We then discuss the unified demonstration of the updated single arm locking, where both the local and the returned laser phase noises can be tuned to generate the expected arm-locking sensor actually. Finally, the time-series simulations in Simulink have been carried out, and the results indicate a good agreement with the theory, showing that the presented method is reasonable and feasible. Our work could provide a back-up strategy for the arm locking in the future space-borne GW detectors.

Effect of Modified Shenling Baizhusan on Gastrointestinal Dysfunction and Protein-energy Wasting in Continuous Ambulatory Peritoneal Dialysis Patients / 中国实验方剂学杂志

ObjectiveTo observe and analyze the effect of modified Shenling Baizhusan on gastrointestinal dysfunction and protein-energy wasting （PEW） of continuous ambulatory peritoneal dialysis （CAPD） patients with the syndrome of spleen deficiency， blood stasis， and dampness. MethodA total of 66 CAPD patients with the above syndrome were randomized into the observation group and control group， 33 cases in each group. However， 3 cases in each group dropped out， finally leaving 30 cases in each group. Both groups received CAPD and conventional symptomatic treatment. On this basis， the observation group was given modified Shenling Baizhusan （1 bag/day， once in the morning and again in the evening， 12 weeks）， and the control group the bifidobacterium capsules （1.05 g/time， twice/day， 12 weeks）. Before and after treatment， the traditional Chinese medicine （TCM） syndrome score， gastrointestinal symptom rating scale （GSRS） score， and malnutrition-inflammation score （MIS） in two groups were recorded， and the levels of serum albumin （ALB）， prealbumin （PA）， transferrin （TRF）， gastrin-17 （G-17）， tumor necrosis factor alpha （TNF-α）， interferon-γ （IFN-γ）， and interleukin-10 （IL-10） were detected. Moreover， body mass index （BMI） was calculated. ResultAfter treatment， the alleviation of the TCM syndrome in the observation group was better than that in the control group （Z=-2.591， P<0.05）， and the TCM syndrome score in the observation group was lower than that in the control （P<0.05）. The symptom scores， MIS， and G-17 of the observation group were significantly decreased compared with those before observation and in the control group （P<0.05）. After treatment， the GSRS scores of the two groups were significantly lower than those before treatment （P<0.05）， particularly the observation group （P<0.05）. ALB， PA， TRF， and BMI of the observation group after treatment were increased compared with those before treatment and those of the control group after treatment （P<0.05）. After treatment， serum TNF-α and IFN-γ of the two groups were significantly reduced compared with those before treatment （P<0.05）， and the levels of the two in the observation group were significantly lower in the observation group than in the control group （P<0.05）. After treatment， IL-10 level of the observation group was higher than that before treatment and in the control group （P<0.05）. ConclusionThe modified Shenling Baizhusan can relieve the gastrointestinal dysfunction and PEW in CAPD patients with the syndrome of spleen deficiency， blood stasis， and dampness.

[Exploration on rationality evaluation approach of drug combination medication based on sequential analysis and machine learning].

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.

Taurine improves the differentiation of neural stem cells in fetal rats with intrauterine growth restriction via activation of the PKA-CREB-BDNF signaling pathway.

Intrauterine growth restriction (IUGR) affects brain neural stem cell (NSC) differentiation. In the present study, we investigated whether taurine supplementation may improve NSC differentiation in IUGR fetal rats via the protein kinase A-cyclic adenosine monophosphate (cAMP) response element protein-brain derived neurotrophic factor (PKA-CREB-BDNF) signaling pathway. The IUGR fetal rat model was established with a low-protein diet. Fresh subventricular zone (SVZ) tissue from the fetuses on the 14th day of pregnancy was microdissected and dissociated into single-cell suspensions, then was cultured to form neurospheres. The neurospheres were divided into the control group, the IUGR group, the IUGR+taurine (taurine) group, the IUGR+H89 (H89) group and the IUGR+taurine+H89 (taurine+H89) group. The mRNA and protein expression levels of PKA, CREB and BDNF were measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB). Tuj-1-positive neurons and GFAP-positive glial cells were detected by immunofluorescence. The total number of proliferating NSCs and the percentage of Tuj-1-positive neurons in the IUGR group were lower than those in the control group, but the percentage of GFAP-positive cells was higher in the IUGR group than in the control group. Taurine supplementation increased the total number of neural cells and the percentage of Tuj-1-positive neurons, and reduced the percentage of GFAP-positive cells among differentiated NSCs after IUGR. H89 reduced the total number and percentage of Tuj-1-positive neurons and increased the percentage of GFAP-positive cells. The mRNA and protein levels of PKA, CREB, and BDNF were lower in the IUGR group. The mRNA and protein expression levels of these factors were increased by taurine supplementation but reduced by the addition of H89. Taurine supplementation increased the ratio of neurons to glial cells and prevented gliosis in the differentiation of NSCs in IUGR fetal rats by activating the PKA-CREB-BDNF signaling pathway.

A comprehensive review on traditional uses, chemical compositions, pharmacology properties and toxicology of Tetrastigma hemsleyanum.

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg (T.hemsleyanum), a rare herbal plant distributed in subtropical areas of mainland China, has become a focus of scientific attention in recent years because of its high traditional value, including uses for treatment of children with fever, pneumonia, asthma, rheumatism, hepatitis, menstrual disorders, scrofula, and pharynx pain. AIM: This systematic review aims to provide an insightful understanding of traditional uses, chemical composition, pharmacological effect and clinical application of T. hemsleyanum, and lay a foundation for the further study and for the utilization of T. hemsleyanum resource. MATERIALS AND METHODS: A domestic and overseas literature search in known databases was conducted for published articles using the relevant keywords. RESULTS: One hundred and forty-two chemical constituents identified from T. hemsleyanum have been reported, including flavonoids, phenolic acids, polysaccharide, organic acids, fatty acids, terpenoids, steroids, amino acid and others. Among these components, flavonoids and polysaccharides were the representative active ingredients of T. hemsleyanum, which have been widely investigated. Modern pharmacological studies have shown that these components exhibited various pharmacological activities, such as anti-inflammatory, antioxidant, antivirus, antitumor, antipyretic, anti-hepatic injury, immunomodulatory, antibacterial etc. Moreover, different toxicological studies indicated that the clinical dosage of T. hemsleyanum was safe and reliable. CONCLUSIONS: Modern pharmacological studies have well supported and clarified some traditional uses, and T. hemsleyanum has a good prospect for the development of new drugs due to these outstanding properties. However, the present findings did not provide an in-depth evaluation of bioactivity of the extracts, the composition of its active extracts was not clear. Moreover, they were insufficient to satisfactorily explain some mechanisms of action. Data regarding many aspects of T. hemsleyanum, such as links between the traditional uses and bioactivities, pharmacokinetics, quality control standard and the clinical value of active compositions is still limited which need more attention.

Change in late sodium current of atrial myocytes in spontaneously hypertensive rats with allocryptopine treatment.

AIM: We aimed to study the effect of allocryptopine (All) on the late sodium current (INa,Late) of atrial myocytes in spontaneously hypertensive rats (SHR). METHODS: The enzyme digestion method was used to separate single atrial myocytes from SHR and Wistar-Kyoto (WKY) rats. INa,Late was recorded using the patch-clamp technique, and the effect of All was evaluated on the current. RESULTS: Compared with WKY rat cells, an increase in the INa,Late current in SHR myocytes was found. After treatment with 30 µM All, the current densities were markedly decreased; the ratio of INa,Late/INa,peak of SHR was reduced by 30 µM All. All reduced INa,Late by alleviating inactivation of the channel and increasing the window current of the sodium channel. Furthermore, INa,Late densities of three SCN5A mutations declined substantially with 30 µM All in a concentration-dependent manner. CONCLUSIONS: The results clearly show that an increase in INa,Late in SHR atrial myocytes was inhibited by All derived from Chinese herbal medicine.

[Research advances on chemical constituents from Calycanthaceae plants and their pharmacological activities].

Calycanthaceae family comprises of four genera including Chimonanthus, Sinocalycanthus, Calycanthus, and Idiospermum. The plants of Calycanthaceae are popular ornamental shrubs and used as foods and medicines, which are mainly distributed in China, North America, and Australia. The plants of Calycanthaceae are rich in volatile components, alkaloids, sesquiterpenes and coumarins. Dimeric piperidinoquinoline and dimeric pyrrolidinoindoline alkaloids, dimeric and/or trimeric coumarins are characteristic compositions in these plants. In order to provide timely reference for further investigation and development of Calycanthaceae plants, we made a systemic review on chemical constituents, i.e. alkaloids, terpenoids, flavonoids, coumarins, and steroids, from Calycanthaceae plants, focusing on their chemical structures and pharmacological activities.

Butyrate stimulates the growth of human intestinal smooth muscle cells by activation of yes-associated protein.

Intestinal smooth muscle cells play a critical role in the remodeling of intestinal structure and functional adaptation after bowel resection. Recent studies have shown that supplementation of butyrate (Bu) contributes to the compensatory expansion of a muscular layer of the residual intestine in a rodent model of short-bowel syndrome (SBS). However, the underlying mechanism remains elusive. In this study, we found that the growth of human intestinal smooth muscle cells (HISMCs) was significantly stimulated by Bu via activation of Yes-Associated Protein (YAP). Incubation with 0.5 mM Bu induced a distinct proliferative effect on HISMCs, as indicated by the promotion of cell cycle progression and increased DNA replication. Notably, YAP silencing by RNA interference or its specific inhibitor significantly abolished the proliferative effect of Bu on HISMCs. Furthermore, Bu induced YAP expression and enhanced the translocation of YAP from the cytoplasm to the nucleus, which led to changes in the expression of mitogenesis genes, including TEAD1, TEAD4, CTGF, and Cyr61. These results provide evidence that Bu stimulates the growth of human intestinal muscle cells by activation of YAP, which may be a potential treatment for improving intestinal adaptation.

Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy.

OBJECTIVE: To evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN). METHODS: Forty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope. RESULTS: Compared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05). CONCLUSIONS: Tangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.

Therapeutic Role of Tangshenkang Granule () in Rat Model with Diabetic Nephropathy / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the renal protective effect of Tangshenkang Granule () in a rat model of diabetic nephropathy (DN).</p><p><b>METHODS</b>Forty male Sprague-Dawley rats were randomly divided into control, DN, Tangshenkang and benazepril groups. DN model was established in the rats of DN, Tangshenkang and benazepril groups. Tangshenkang Granule solution and benazepril hydrochloride solution were intragastrically administered daily to the rats in the Tangshenkang and benazepril groups for 8 weeks, respectively. Urinary albumin and creatinine were detected. The albumin/creatinine (ACR) was calculated in addition to 24 h urinary protein (24-h UPr), serum creatinine (Scr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and creatinine clearance rate (Ccr). Right kidneys were harvested for pathological observation using periodic acid-silver methenamine-Masson staining. The average glomerular diameter (DG), average glomerular (AG) and mesangial areas (AM) were measured. The thickness of glomerular basement membrane (TGBM) was detected using transmission electron microscope.</p><p><b>RESULTS</b>Compared with rats in the control group, rats in the DN group showed significantly decreased body weight, increased hypertrophy index, 24-h urinary volume, 24-h UPr, ACR, Scr, BUN, Ccr, blood lipids as well as renal pathological indices including DG, AG, AM, AM/AG and TGBM (P <0.05). Compared with the DN group, the weights of rats in the Tangshenkang and benazepril groups were significantly increased, and the renal hypertrophy indices were significantly decreased (P <0.05). The 24-h urinary volumes, ACR, 24-h UPr, Scr, BUN, Ccr, LDL, DG, AG, AM and TGBM were obviously decreased (P <0.05). Compared with the benazepril group, the Tangshenkang group showed significantly decreased levels of ACR, 24-h UPr, AG and AM (P <0.05).</p><p><b>CONCLUSIONS</b>Tangshenkang Granule decreased the urinary protein, attenuated the high glomerular filtration rate and improved lipid metabolism in DN rats, and prevented further injury induced by diabetic nephropathy.</p>

[Intervention of Qingshen Granule on NF-KB Signal Pathway of Chronic Renal Failure Patients with Damp-heat Syndrome].

Objective To observe the effect of Qingshen Granule (QG) on expressions of nucle- ar factors-κB p65 (NF-κB p65) and phosphonated inhibitor of nuclear factor-κB (p-lκBα) in peripheral blood NF-κB signal transduction pathway of chronic renal failure (CRF) patients with damp-heat syn- drome (DHS) , and to study possible mechanism. Methods Totally 68 CRF patients with DHS were as- signed to the control group and the treatment group by random digit table, 34 in each group. Actually 63 patients completed, 32 in the treatment group and 31 in the control group. A normal group (20 cases) was set up. All patients received basic treatment of Western medicine (WM) and retention enema of Chi- nese medicine (CM). Patients in the treatment group additionally took QG, 1 package each time, 3 times per day. The therapeutic course for all was 8 weeks. The clinical efficacy, level of serum creatinine (SCr), estimated glomerular filtration rate (eGFR), the levels of NF-κB p65 and p-IκBα in peripheral blood were observed and measured before and after treatment. They were also compared with those of the normal group. Results The clinical efficacy and the total effective rate of CM syndrome were 84. 38% (27/32)and 81. 25% (26/32), superior to those of the control group [54. 84%(17/31), 51. 61% (1631) ; P <0. 01 ]. Compared with before treatment, the level of SCr was obviously lower, and eGFR was obviously higher in the treatment group after treatment (P <0. 01). They were better than those of the control group after treatment (P <0. 05). Compared with the normal group, the levels of NF-κB p65 and p-IκBα were significantly higher in the treatment group and the control group before treatment (P < 0. 01). Compared with before treatment, the levels of NF-κB p65 and p-IκBα were obviously lowered in the treatment group after treatment (P <0. 01). They were also better than those of the control group after treatment (P <0. 05). Conclusions QG could improve clinical symptoms of CRF patients with DHS, de- crease SCr level, and increase eGFR level. It could protect renal function. Its mechanism might possibly be related with reducing peripheral blood levels of NF-κB p65 and p-IκBα.

Antibody-Based Drugs and Approaches Against Amyloid-ß Species for Alzheimer's Disease Immunotherapy.

Alzheimer's disease (AD), one of the most devastating diseases for the older population, has become a major healthcare burden in the increasingly aging society worldwide. Currently, there are still only symptomatic treatments available on the market, just to slow down disease progression. In the past decades, extensive research focusing on the development of immunotherapy using monoclonal antibodies (mAbs) as potential "disease-modifying drugs" has shown promise in inhibiting or clearing the formation of toxic amyloid-ß (Aß) species, the suspected causative agents of AD. As a result, these potential life-saving drugs can break the amyloid cascade, cease neurodegeneration, and prevent further reduction in cognitive and physical function. In this review, we first describe the polymorphisms of Aß species, comprising three different pools, including monomers, soluble oligomers, and insoluble fibrils, with each pool encompassing multiple structures of Aß aggregation. A comprehensive review on their toxicities follows in relation to the characterized epitopes of anti-Aß mAb candidates under development. We then present the outcomes of these mAbs in clinical or pre-clinical trials and conclude by providing a summary of other novel and promising antibody-based immunotherapeutic approaches that deserve more attention for the effective treatment of AD in the future.

Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway.

BACKGROUND AND AIMS: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. METHODS: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. RESULTS: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. CONCLUSIONS: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.

A monomer purified from Paris polyphylla (PP-22) triggers S and G2/M phase arrest and apoptosis in human tongue squamous cell carcinoma SCC-15 by activating the p38/cdc25/cdc2 and caspase 8/caspase 3 pathways.

Recent studies have shown that the aqueous, ethanolic extracts and a monomer compound of Paris polyphylla exhibit anticancer activity toward several types of cancer cell lines, but the anticancer activity of (3ß,17α,25R)-spirost-5-ene-3,17-diol 3-O-α-L-rhamnopyranosyl-(1 â†’ 2)-ß-D-glucopyranoside, a monomer isolated from P. polyphylla (PP), named PP-22, has not been reported previously. In this study, we investigated the effect of PP-22 on human tongue squamous cell carcinoma SCC-15 cells in vitro. MTT assays showed that PP-22 inhibited the growth of SCC-15 cells and had no obvious inhibitory effects on human liver L02 cells. Flow cytometry assays showed that the percentages of apoptotic cells were increased. In addition, cleaved caspase-8, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) could be detected by Western blotting. Flow cytometry also showed that PP-22 triggered S and G2/M phases arrest in SCC-15 cells, and on the other hand, the expression of cyclin A, cyclin E2, cyclin B1, phospho-cell division cycle2 (p-cdc2)(Tyr15), p-Wee1, Myt1, and p53 was upregulated. Moreover, p-p38 levels increased, p-extracellular signal-regulated kinase (ERK) levels decreased, and cdc25B expression was inhibited. Furthermore, the p38/mitogen-activated protein kinase (MAPK) inhibitor SB203580 reversed the increase of the expression level of p38, p-cdc2 (Tyr15), cleaved caspase 3, cleaved PARP, p-p53, and p53 and reversed the decrease in cdc25B expression. In conclusion, these results demonstrated that PP-22 activated p38, inhibited cdc25B, increased p-cdc2 (Tyr15), and triggered S and G2/M phase arrest, as well as activated p53 through the p38-p53 pathway, inhibited the MAPK/ERK pathway, activated the caspase 8/caspase 3 pathway, and triggered the extrinsic apoptotic pathway in SCC-15 cells.

Effect of an Olive Oil-Based Lipid Emulsion Compared With a Soybean Oil-Based Lipid Emulsion on Liver Chemistry and Bile Acid Composition in Preterm Infants Receiving Parenteral Nutrition: A Double-Blind, Randomized Trial.

BACKGROUND: The pathogenesis of parenteral nutrition (PN)-associated liver dysfunction is multifactorial. Lipid emulsions may be one of the putative mechanisms. Our aim was to comparatively assess the effect of parenteral olive oil- and soybean oil-based lipid emulsions on liver chemistry and bile acid composition in preterm infants. METHODS: We performed a double-blind, randomized clinical study in which 103 preterm infants were randomly assigned to PN using either soybean oil-based lipid emulsion (SO; n = 51) or olive oil (OO)-based lipid emulsion (OO; n = 52). The primary end point was liver chemistry. The secondary end point was the plasma bile acid composition. RESULTS: One hundred infants completed this study. In the SO group, the serum direct bilirubin was significantly higher after PN for 7 days compared with the OO group. Bile acids increased over time in both treatment groups. However, specific differences in the change in bile acid composition over time were noted between groups. CONCLUSIONS: Differences in direct bilirubin and bile acid composition were observed over time between the 2 groups. Considering the long-term use of lipid emulsions in higher risk babies, these findings might be useful for understanding the pathogenesis of PN-associated liver dysfunction.

Therapeutic Potential of Steroidal Alkaloids in Cancer and Other Diseases.

Steroidal alkaloids are a class of secondary metabolites isolated from plants, amphibians, and marine invertebrates. Evidence accumulated in the recent two decades demonstrates that steroidal alkaloids have a wide range of bioactivities including anticancer, antimicrobial, anti-inflammatory, antinociceptive, etc., suggesting their great potential for application. It is therefore necessary to comprehensively summarize the bioactivities, especially anticancer activities and mechanisms of steroidal alkaloids. Here we systematically highlight the anticancer profiles both in vitro and in vivo of steroidal alkaloids such as dendrogenin, solanidine, solasodine, tomatidine, cyclopamine, and their derivatives. Furthermore, other bioactivities of steroidal alkaloids are also discussed. The integrated molecular mechanisms in this review can increase our understanding on the utilization of steroidal alkaloids and contribute to the development of new drug candidates. Although the therapeutic potentials of steroidal alkaloids look promising in the preclinical and clinical studies, further pharmacokinetic and clinical studies are mandated to define their efficacy and safety in cancer and other diseases.

[Effects of Enhanced Ultraviolet B Irradiation on Photosynthetic and Antioxidant System of Sorghum Seedlings].

The UV-B radiation on the surface of our planet has been enhanced due to gradual thinning of ozone layer. The change of solar spectrum UV-B radiation will cause damage to all kinds of terrestrial plants at certain degree. In this paper, taking breeding sorghum (Sorghum bicolor (L.Moench))variety Longza No.5 as sample, 40 µW·cm-2 UV-B radiation treatment was conducted on sorghum seedlings at two-leaf and one-heart stage and different time courses; then after a 2 d recovering, photosynthetic parameters were measured with a photosynthetic apparatus; the activities of antioxidant enzymes were detected as well. Our results revealed that, as the dosages of UV-B increasing, leaf browning injury was aggravated, plants dwarfing and significantly were reduced fresh weight and dry weight were observed; anthocyanin content was significantly increased; chlorophyll and carotenoid content significantly were reduced and net photosynthetic rate and chlorophyll fluorescence parameters were decreased. Meanwhile, with the increase in UV-B dosages, stomatal conductance, intercellular CO2 concentration and transpiration rate showed "down - up - down" trend; the activities of SOD and GR presented "down - up" changes; activities of POD and CAT demonstrated "down - up - down", and APX, GPX showed an "up - down - up" pattern. It is worth to note that, under the four-dose treatment, a sharp decline in net photosynthesis in sorghum seedlings was observed at 6 h UV-B treatment (equals to 2.4 J·m-2), and an obvious turning point was also found for other photosynthetic parameters and activities of antioxidant enzymes at the same time point. In summary, the results indicated that the enhanced UV-B radiation directly accounted for the damages in photosynthesis system including photosynthetic pigment content, net photosynthetic rate and chlorophyll fluorescence parameters of sorghum; the antioxidant system showed different responses to UV-B radiation below or above 6 h treatment: ASA-GSH cycle was more sensitive to low-dose UV-B radiation, while high-dose UV-B radiation not only undermined the photosynthesis system, but also triggered plant enzymatic and non-enzymatic antioxidant systems, resulting in leaf browning and necrosis,biomass accumulation reduction, plant dwarfing and even death.

Synergistic anticancer effects of triptolide and celastrol, two main compounds from thunder god vine.

Triptolide and celastrol are two main active compounds isolated from Thunder God Vine with the potent anticancer activity. However, the anticancer effect of triptolide in combination with celastrol is still unknown. In the present study, we demonstrated that the combination of triptolide with celastrol synergistically induced cell growth inhibition, cell cycle arrest at G2/M phase and apoptosis with the increased intracellular ROS accumulation in cancer cells. Pretreatment with ROS scavenger N-acetyl-L-cysteine dramatically blocked the apoptosis induced by co-treatment with triptolide and celastrol. Treatment with celastrol alone led to the decreased expressions of HSP90 client proteins including survivin, AKT, EGFR, which was enhanced by the addition of triptolide. Additionally, the celastrol-induced expression of HSP70 and HSP27 was abrogated by triptolide. In the nude mice with xenograft tumors, the lower-dose combination of triptolide with celastrol significantly inhibited the growth of tumors without obvious toxicity. Overall, triptolide in combination with celastrol showed outstanding synergistic anticancer effect in vitro and in vivo, suggesting that this beneficial combination may offer a promising treatment option for cancer patients.