PAMK Relieves LPS-Induced Enteritis and Improves Intestinal Flora Disorder in Goslings.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a biologically active component of Atractylodes macrocephala, which has the effect of maintaining the immune homeostasis of the body. Therefore, this study constructed a model of PAMK to relieve LPS-induced gosling enteritis and observed the morphological changes of the small intestine after HE staining. ELISA was used to detect serum CRP, IL-1ß, IL-6, and TNF-α levels; immunohistochemistry was used to detect the positive rate of IgA in the small intestine; TLR4, occludin, ZO-1, cytokines, and immunoglobulin mRNA expression in the small intestine were detected by qPCR; and intestinal flora of gosling excrement was analyzed by 16S rDNA sequencing to analyze the protective effect of PAMK on goslings enteritis and the impact on intestinal flora. The results showed that PAMK relieves LPS-induced gosling enteritis by maintaining the small intestine morphology, cytokine, tight junctions, and immunoglobulin relatively stable and improving the disorder of intestinal flora.

Repair of Tea Polysaccharide Promotes the Endocytosis of Nanocalcium Oxalate Monohydrate by Damaged HK-2 Cells.

Endocytosis is a protective mechanism of renal epithelial cells to eliminate retained crystals. This research investigated the endocytosis of 100 nm calcium oxalate monohydrate crystals in human kidney proximal tubular epithelial (HK-2) cells before and after repair by four kinds of tea polysaccharides with molecular weights (MWs) of 10.88 (TPS0), 8.16 (TPS1), 4.82 (TPS2), and 2.31 kDa (TPS3), respectively. When HK-2 cells were repaired by TPSs after oxalic acid injury, the cell viability, wound healing ability, mitochondrial membrane potential, percentage of cells with endocytosed crystals, and dissolution rate of the endocytosed crystals increased; the cell morphology recovered; and the reactive oxygen level and lactate dehydrogenase release decreased. Most of the endocytosed crystals were found in the lysosomes. The repair effects of the four TPSs were ranked in the following order: TPS2>TPS1>TPS3>TPS0. TPS2 with moderate MW presented the optimal repair ability and strongest ability to promote endocytosis.

Selenium-Alleviated Hepatocyte Necrosis and DNA Damage in Cyclophosphamide-Treated Geese by Mitigating Oxidative Stress.

Selenium (Se) has been well recognized as an immune-enhancing agent with antioxidant and anti-tumor properties. The commonly used chemotherapy drug, cyclophosphamide (CTX), induces liver injury by increasing the reactive oxygen species (ROS) level. However, little is known about how Se alleviates CTX-induced liver injury in geese. In this study, 90 male Magang geese (3 days old) were randomly allocated into three groups (control, CTX, and Se + CTX group) with three replicates per group and ten geese per replicate. The control and CTX groups were fed a basal diet (Se content was 0.03 mg/kg). The Se + CTX group was fed a basal diet containing 0.44 mg/kg sodium selenite (Se content was 0.2 + 0.03 mg/kg). The control group was injected with 0.5 mL saline, while the CTX and Se + CTX groups were injected with CTX at 40 mg/kg body weight per day on days 21-23. The liver index, liver histology, and ultra-micromorphology detected antioxidant enzyme activity in the liver and serum. In addition, we detected the liver marker enzymes and protein levels in serum, and hepatocyte DNA damage. Se could alleviate liver development dysregulation, hepatocyte structural damage, the disturbances in antioxidant enzyme (GPx, CAT, and SOD) activity, and malondialdehyde (MDA) levels in the serum and liver. Besides, Se could alleviate the dysregulation of liver marker enzyme (ALT and AST) activity and protein (ALB and TP) levels in the serum, and DNA migration induced by CTX. In conclusion, Se may inhibit hepatocyte necrosis and DNA damage by inhibiting CTX-induced oxidative stress.

Identification of Aloperine as an anti-apoptotic Bcl2 protein inhibitor in glioma cells.

OBJECTIVE: Aloperine (ALO), an alkaloid isolated from the leaves of Sophora alopecuroides, has been suggested to exhibit anti-inflammatory and anti-tumor properties and is traditionally used to treat various human diseases, including cancer. However, limited information is available about the mechanisms that determine the anti-tumor activities of ALO. METHODS: Herein, through comprehensive bioinformatics methods and in vitro functional analyses, we evaluated the detailed anti-tumor mechanisms of ALO. RESULTS: Using the databases Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine and PubChem Project, we identified the potential targets of ALO. A protein-protein interaction network was constructed to determine the relationship among these probable targets. Functional enrichment analysis revealed that ALO is potentially involved in the induction of apoptosis. In addition, molecular docking demonstrated that ALO expectedly docks into the active pocket of the Bcl2 protein, suggesting Bcl2 as a direct target of ALO. Moreover, western blot and qPCR analysis showed that ALO downregulated Bcl2 expression in human glioma cell lines, SK-N-AS and U118. Using flow cytometry methods, we further confirmed that ALO significantly promotes apoptosis in SK-N-AS and U118 cell lines, similar to the effect induced by ABT-737, a well-known Bcl2 inhibitor. In addition, Bcl-2 overexpression could rescue ALO-induced Bcl-2 inhibition and suppress pro-apoptotic effects in glioma cells. CONCLUSION: Taken together, these findings suggest that the natural agent ALO effectively enhances apoptosis by acting as a potential Bcl2 inhibitor in human glioma cells.

The Antitumor Activities of Marsdenia tenacissima.

Marsdenia tenacissima (MT), a traditional Chinese herbal medicine, has long been used for thousands of years to treat asthma, tracheitis, rheumatism, etc. An increasing number of recent studies have focused on the antitumor effects of MT. The effects of MT on cancer are the result of various activated signaling pathways and inhibiting factors and the high expression levels of regulatory proteins. MT can inhibit different cancer types including non-small cell lung cancer (NSCLC), malignant tumors, hepatic carcinoma, and so on. This article mainly focuses on the activities and mechanisms of MT. In addition, the efficacy and toxicity of MT are also discussed. Further studies of MT are required for improved medicinal utilization.

A Genetically Encoded Protein Polymer for Uranyl Binding and Extraction Based on the SpyTag-SpyCatcher Chemistry.

A defining goal of synthetic biology is to develop biomaterials with superior performance and versatility. Here we introduce a purely genetically encoded and self-assembling biopolymer based on the SpyTag-SpyCatcher chemistry. We show the application of this polymer for highly efficient uranyl binding and extraction from aqueous solutions, by embedding two functional modules-the superuranyl binding protein and the monomeric streptavidin-to the polymer via genetic fusion. We further provide a modeling strategy for predicting the polymer's physical properties, and experimentally demonstrate the autosecretion of component monomers from bacterial cells. The potential of multifunctionalization, in conjunction with the genetic design and production pipeline, underscores the advantage of the SpyTag-SpyCatcher biopolymers for applications beyond trace metal enrichment and environmental remediation.

Advances in immunotherapy of Alzheimer's disease with traditional Chinese medicine / 药学学报

Alzheimer's disease (AD) is a type of common neurodegenerative disease. The main clinical symptom of the disease is progressive cognitive dysfunction, which has no effective therapy yet. With the in-depth immunology study in the central nervous system, studies in different fields such as preclinical phase, genetics and bioinformatics have shown that immune dysfunction contribute to the pathogenesis of AD, including the beginning, maintenance and deterioration stage in AD. China has a wealth of natural medicine resources and clinical experiences. A large number of natural drugs and effective components both can regulate the immune function and ameliorate the symptoms in AD. This review summarizes the researches of ameliorating the symptoms in AD through immunization regulation in recent years with an aim to provide new ideas and clues in the study of new anti-AD drugs using natural medicines.

Radiosensitizing effect of diosmetin on radioresistant lung cancer cells via Akt signaling pathway.

Radiotherapy is a powerful tool in the treatment of cancer that has the advantage of preserving normal tissues. However, tumor radioresistance currently remains a major impediment to effective RT. Thus, exploring effective radiation sensitizers is urgently needed. In this study, we have shown that diosmetin, the aglycone of the lavonoid glycoside from olive leaves, citrus fruits and some medicinal herbs, has a promising effect on radiotherapy sensitization. In our results, DIO could induce G1 phase arrest and thus enhance the radiosensitivity of radioresistant A549/IR lung cancer cells. Furthermore, DIO also restrains the IR-induced DNA damage repair by inhibiting the activated Akt signaling pathway. The combination of Akt inhibition (DIO, LY294002 or MK-2206) and radiation potently blocked A549/IR cancer cell proliferation. In summary, these observations suggest that the natural compound DIO could act as a potential drug for the treatment of radioresistant lung cancer cells.

Electroacupuncture pretreatment induces rapid tolerance to bupivacaine cardiotoxicity in rats.

BACKGROUND: Evidence suggests that electroacupuncture (EA) protects against arrhythmia and myocardial injury induced by myocardial ischaemia-reperfusion. However, to our knowledge, it remains unknown whether EA could alleviate bupivacaine-induced cardiotoxicity. Therefore, we aimed to explore the effect of EA pretreatment on bupivacaine-induced cardiac arrest and outcomes of cardiopulmonary resuscitation (CPR) in rats. METHODS: 24 adult male Sprague-Dawley rats were randomly divided into two groups: EA (n=12), and minimal acupuncture (MA) (n=12). Rats in both groups were needled at bilateral PC6, ST36, and ST40. Needles in the EA group were electrically stimulated for 60 min. ECG and invasive arterial blood pressure measurements were recorded. Two hours after EA or MA, 10 mg/kg bupivacaine was infused intravenously at a rate of 5 mg/kg/min in all rats. Rats suffering cardiac arrest were immediately subjected to CPR. At the end of the experiment, arterial blood samples were taken from surviving rats for blood gas analysis. RESULTS: The time from bupivacaine infusion until 20% prolongation of the QRS and QT interval, and the time to cardiac arrest, were notably increased among the rats pretreated with EA. Moreover, EA pretreatment significantly improved mean arterial pressure and heart rate at all monitored points after bupivacaine infusion. The proportion of animals surviving was higher in the EA group (9/12) than the MA group (3/12) at the end of experiment (p=0.039). CONCLUSIONS: Tolerance to bupivacaine-induced cardiotoxicity appeared to be increased following EA pre-treatment. The mechanism of action underlying the effects of EA on bupivacaine-induced cardiotoxicity requires further investigation.

Effects on decreasing upper-limb poststroke muscle tone using transcranial direct current stimulation: a randomized sham-controlled study.

OBJECTIVE: To assess the efficacy of transcranial direct current stimulation (tDCS) on decreasing upper-limb (UL) muscle tone after stroke. DESIGN: A prospective, sham-controlled, randomized controlled trial with 4-weeks follow-up. Randomization into the tDCS group or the control group. SETTING: Rehabilitation education and research hospital. PARTICIPANTS: Inpatients (N=90, 45 per group; age range, 15-70y; 69 men, 21 women; duration of stroke, 2-12mo) with poststroke UL spasticity. No participant withdrew because of adverse effects. INTERVENTION: The tDCS group received tDCS to the primary sensorimotor cortex of the affected side with cathodal stimulation, 20 minutes per day, 5 days per week, for 4 weeks and conventional physical therapy. The control group received sham stimulation (same area as the tDCS group) and conventional physical therapy. MAIN OUTCOME MEASURES: Modified Ashworth scale (MAS), Fugl-Meyer Assessment of motor recovery, and Barthel Index. All outcomes were measured at admission, after treatment, and after follow-up. A clinically important difference (CID) was defined as a reduction of ≥1 in the MAS score. RESULTS: Compared with the sham tDCS group, the active tDCS group had significantly more patients with a clinically important difference after treatment (80% and 78% vs 6% and 9%) and at 4-week follow-up (84% and 82% vs 7% and 4%), and UL motor function and activities of daily living (ADL) assessment improved more significantly in the active tDCS group (Fugl-Meyer Assessment of motor recovery from 12 [range, 4-26] to 22 [range, 7-50] to 32 [range, 28-41], Barthel Index from 55 [range, 0-85] to 85 [range, 5-100] to 90 [range, 10-100 vs Fugl-Meyer Assessment of motor recovery from 8 [range, 3-34] to 10 [range, 8-25] to 15 [range, 6-40], Barthel Index from 55 [range, 25-95] to 65 [range, 30-100] to 75 [range, 40-100], respectively, P<.01). CONCLUSIONS: UL muscle tone after stroke can be decreased using cathodal tDCS. Combined with conventional physical therapy, tDCS appears to improve motor function and ADL. Cathodal tDCS over ipsilesional primary sensorimotor cortex may inhibit primary sensorimotor cortex hyperactivation, resulting in significant reductions in muscle tone.