Potential anticoagulant of traditional chinese medicine and novel targets for anticoagulant drugs.

BACKGROUND: Anticoagulants are the main drugs used for the prevention and treatment of thrombosis. Currently, anticoagulant drugs are primarily multitarget heparin drugs, single-target FXa inhibitors and FIIa inhibitors. In addition, some traditional Chinese drugs also have anticoagulant effects, but they are not the main direction of treatment at present. But the anticoagulant drugs mentioned above, all have a common side effect is bleeding. Many other anticoagulation targets are under investigation. With further exploration of coagulation mechanism, how to further determine new anticoagulant targets and how to make traditional Chinese medicine play anticoagulant role have become a new field of exploration. PURPOSE: The purpose of the study was to summarize the recent research progress on coagulation mechanisms, new anticoagulant targets and traditional Chinese medicine. METHODS: A comprehensive literature search was conducted using four electronic databases, including PubMed, Embase, CNKI, Wanfang database and ClinicalTrials.gov, from the inception of the study to 28 Feb 2023. Key words used in the literature search were "anticoagulation", "anticoagulant targets", "new targets", "coagulation mechanisms", "potential anticoagulant", "herb medicine", "botanical medicine", "Chinese medicine", "traditional Chinese medicine", "blood coagulation factor", keywords are linked with AND/OR. Recent findings on coagulation mechanisms, potential anticoagulant targets and traditional Chinese medicine were studied. RESULTS: The active components extracted from the Chinese medicinal herbs, Salvia miltiorrhiza, Chuanxiong rhizoma, safflower and Panax notoginseng have obvious anticoagulant effects and can be used as potential anticoagulant drugs, but the risk of bleeding is unclear. TF/FVIIa, FVIII, FIX, FXI, FXII, and FXIII have all been evaluated as targets in animal studies or clinical trials. FIX and FXI are the most studied anticoagulant targets, but FXI inhibitors have shown stronger advantages. CONCLUSION: This review of potential anticoagulants provides a comprehensive resource. Literature analysis suggests that FXI inhibitors can be used as potential anticoagulant candidates. In addition, we should not ignore the anticoagulant effect of traditional Chinese medicine, and look forward to more research and the emergence of new drugs.

Therapeutic and Neuroprotective Effects of Bushen Jianpi Decoction on a Rotenone-Induced Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Dopamine (DA) replacement therapy is one of the most effective drug treatments for PD; however, long-term levodopa treatment can lead to various side effects that negatively impact the quality of life of patients. Therefore, finding safe and effective alternative drugs to treat PD is of clinical importance. The Bushen-Jianpi decoction (BSJPD) was derived from classic traditional Chinese medicine and has been shown to be effective in the treatment of PD. This study explored the effects and mechanisms of action of BSJPD in PD. In our study, rats were randomly divided into six groups: the vehicle group, rotenone (ROT) + Saline group, ROT + low-dose BSJPD group, ROT + high-dose BSJPD group, ROT + Madopar group, and ROT + low-dose BSJPD + Madopar group. Treatment was administered to the rats once a day for 28 days, and behavioral tests were assessed. Tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), dopa decarboxylase (DDC), alpha-synuclein (α-syn), and heme oxygenase-1 (HO-1) levels were detected. Our results show that BSJPD increases the body weight of rats, improves their motor coordination, reverses decreasing TH levels in the SN, and increases the expression level of DDC and HO-1 in the striatum (ST), but it fails to affect TH levels in the ST in the PD model. In addition, BSJPD reduced the expression of MAO-B in the ST in the PD model, but it did not have a significant effect on COMT. Rather, COMT in the plasma and liver increased in the low-dose BSJPD treatment group. Upregulation of α-syn in the PD model was also observed, but BSJPD has shown no obvious effect to clear it. Our results suggest that BSJPD exhibits a therapeutic effect on PD and may play a neuroprotective role by regulating HO-1 expression and participating in the metabolic process of DA.

The therapeutic potential of natural products for treating pancreatic cancer.

Pancreatic cancer is one of the most malignant tumors of the digestive tract, with the poor prognosis and low 5-year survival rate less than 10%. Although surgical resection and chemotherapy as gemcitabine (first-line treatment) has been applied to the pancreatic cancer patients, the overall survival rates of pancreatic cancer are quite low due to drug resistance. Therefore, it is of urgent need to develop alternative strategies for its treatment. In this review, we summarized the major herbal drugs and metabolites, including curcumin, triptolide, Panax Notoginseng Saponins and their metabolites etc. These compounds with antioxidant, anti-angiogenic and anti-metastatic activities can inhibit the progression and metastasis of pancreatic cancer. Expecting to provide comprehensive information of potential natural products, our review provides valuable information and strategies for pancreatic cancer treatment.

Effect of acupuncture on long-term outcomes in patients with post-stroke dysphagia.

BACKGROUND: Acupuncture has been used to treat patients with post-stroke neurological dysfunction. OBJECTIVE: The purpose of our observational study was to observe the long-term efficacy of acupuncture and investigate whether the acupuncture treatment could short the recovery time of patients with post-stroke dysphagia. METHODS: Medical records were reviewed to select patients who met the inclusion criteria for post-stroke dysphagia. Exposure factor was defined as received acupuncture during inpatient. Clinical data were obtained at the 6-month follow-up. The primary outcome was the time to improve the score of Food Intake Level Scale (FILS, 0-10) by 3 grades. Cox regression models were used to assess the relationship between acupuncture and recovery of dysphagia. RESULTS: In acupuncture group, the median time to achieve clinical improvement of dysphagia was 97 days (95% CI, 93-124) compared with 119 days (95% CI, 108-145) in control group, with a statistically significant difference between the two groups (HR = 1.48; 95% CI 1.14-1.92; P = 0.003). At 6 months, 78 patients (60.5%) in acupuncture group reached excellent function and 61 patients (47.3%) in control group (RR = 1.28; 95% CI, 1.02-1.62; P = 0.045). 106 patients (82.2%) in acupuncture group achieved favorable function and 91 patients (70.5%) in control group (RR = 1.17; 95% CI, 1.02-1.35; P = 0.039). The outcome of adjusted multivariable Cox regression models showed that there was a difference in the recovery time of dysphagia between groups, HR = 1.79, 95% CI 1.34-2.39. The rates of adverse events were similar in both groups. CONCLUSIONS: Acupuncture can promote the recovery of post-stroke dysphagia, and has a better long-term efficacy. Besides, it can reduce the degree of disability and improve the quality of life.

Caudatin Inhibits the Proliferation, Invasion, and Glycolysis of Osteosarcoma Cells via the Wnt/ß- Catenin Pathway.

Background: Caudatin is a steroidal glycoside with reported anticancer activity in a variety of studies. Nevertheless, the role and mechanisms of caudatin in osteosarcoma (OS) remain unclear. In this study, we explored the potential anticancer effects of caudatin in OS cells and investigated the underlying mechanisms. Methods: Both the CCK8 proliferation assay and flow cytometry were employed to evaluate cell proliferation and apoptosis. A transwell assay was applied to determine cell invasion ability. Besides, glycolytic capacity was examined by measuring glucose consumption, lactic acid production, as well as ATP production. A western blot was utilized to assess the protein levels of ß-catenin, CyclinD 1, C-myc, HK2 (Hexokinase 2), LDHA (lactate dehydrogenase), as well as epithelial-mesenchymal transition (EMT)-related markers. The inhibitory effect of caudatin on tumor growth was investigated using a xenograft tumorigenesis model. Results: Caudatin restrained cellular glycolysis, suppressed cell proliferation and invasion by reducing HK2 and LDHA expression and regulating the Wnt/ß-Catenin signaling pathway. Caudatin treatment caused the upregulation of E-cadherin and suppressed N-cadherin expression. Further, caudatin treatment impaired cell viability, invasion ability, and intracellular glycolysis level but induced apoptosis. The administration of BML 284 reversed the inhibitory effects of caudatin. Moreover, caudatin suppressed the tumorigenesis of OS cells in the xenograft model of nude mice. Conclusions: Our study revealed the anticancer effects of caudatin, including proliferation inhibition, cell invasion suppression, and glycolysis impairment. These effects seem to be executed through targeting the Wnt/ß-Catenin signaling pathway. These data indicate that caudatin may be formulated as a potential therapeutic for osteosarcoma.

Combinatorial Synthesis of Novel 1-sulfonyloxy/acyloxyeugenol Derivatives as Fungicidal Agents.

BACKGROUND: Developing the high-efficiency and low-risk small-molecule greenfungicide is the key to effective control of the plant pathogenic oomycetes. Essential oils play a very important role in novel fungicide discovery for their unique sources and potential target sites. Eugenol, a kind of plant essential oil, was mainly isolated from the unopened and dried flower buds of Syzygium aromaticum of the Myrtaceae family. Due to its unique structural skeleton, eugenol and its derivatives have exhibited a wide range of biological activities. However, a study on the synthesis of novel 1-sulfonyloxy/acyloxyeugenol derivatives as fungicidal agents against Phytophthora capsici has not yet been reported. METHODS: Twenty-six novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) were prepared and their structures were well characterized by 1H NMR, HRMS, and m.p. Their fungicidal activity was evaluated against P. capsici by using the mycelial growth rate method. RESULTS: To find novel natural-product-based fungicidal agents to control the plant pathogenic oomycetes, we herein designed and synthesized two series of novel 1-sulfonyloxy/acyloxyeugenol derivatives (3a-p and 5a-j) as fungicidal agents against P. capsici Leonian, in vitro. Results of fungicidal activity revealed that, among all compounds, especially compounds 3a, 3f, and 3n displayed the most potent anti-oomycete activity against P. capsici with EC50 values of 79.05, 75.05, and 70.80, respectively. CONCLUSION: The results revealed that the anti-oomycete activity of eugenol with the sulfonyloxy group was higher than that with the acyloxy group. It is suggested that the fungicidal activity of eugenol can be improved by introducing the sulfonyloxy group. This will pave the way for further design, structural modification, and development of eugenol derivatives as fungicidal agents.

Development and application of a visual microarray for synchronously detecting H5N1, H7N9 and H9N2 avian influenza virus RNA.

The aim of this study was to develop a microarray assay for the simultaneous detection of the H5, H7, H9, N1, N9 and N2 genes of the avian influenza virus (AIV) using a Nanogold-streptavidin and silver-stain-enhanced nucleic acid dot-blot hybridisation system. The conserved sequences of H5 genes from H5N1, H7 genes from H7N9, H9 genes from H9N2, N9 genes from H7N9 and N2 genes from H9N2 AIV were cloned, together with that of N1 obtained commercially, and were used as templates for generating the probes using biotin-labeled primers, which targeted the conserved regions of H5, H7, H9, N1, N9 and N2 genes, respectively. The oligonucleotide probes were diluted using the spotting buffer and ddH2O, and each probe was then spotted to each specific position on the microarray. The PCR products including biotin-labeled lambda, NP, H5, H7, H9, N1, N9 and N2 were mixed, 200 µL of which was then added to the microarray chamber after denaturing. Following a hybridization incubation at 45℃ for 120 min, the microarray was then incubated with nanogold-streptavidin about 4 µg/mL for 30 min. After the supplementary of 200 µL of silver buffer A and silver buffer B in the chamber, the hybridization results were assessed by direct visualization in the dark at room temperature. The microarray assay was optimized and its specificity, sensitivity and stability were evaluated. The optimal conditions comprised a probe concentration of 50 µmol/L, a hybridization temperature of 45℃ and a hybridization time of 2 h. The optimal concentration of nanogold-streptavidin was 4 µg/mL and the optimal staining time was 7 min. The results of specificity evaluation showed that no cross-binding of the probes with each other and no cross-hybridization with Newcastle disease virus, infectious bronchitis virus and infectious laryngotracheitis virus was observed. The optimized microarray assay was significantly more sensitivity than the reverse-transcription PCR assay. The microarray was available after storing at less 90 d at 4 ℃. The optimized microarray assay was validated on clinical specimens and the results showed that it had over 95.6 % correlation with reverse-transcription PCR method. Therefore, the microarray assay could be used for the high throughput detection of AIV infections due to H5N1, H7N9 and H9N2.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Enhancement of Antibacterial and Mechanical Properties of Photocurable ε-Poly-l-lysine Hydrogels by Tannic Acid Treatment.

In this study, a photocurable hydrogel based on an ε-poly-l-lysine (EPL) composite was fabricated by a grafting reaction using glycidyl methacrylate and then complexed with tannic acid (TA) to improve the mechanical stability and antibacterial performance of the EPL hydrogels. UV-visible spectrophotometry, nuclear magnetic resonance, and Fourier transform infrared spectroscopy were introduced to characterize the chemical construction. The obtained EPLMA hydrogel was immersed into TA solution to induce the forming of the H-bond between EPL and TA, resulting in double networks in the composite hydrogel (EPLMA-TA). Due to the additional hydrogen-bond interaction between TA and EPLMA, the mechanical properties of hydrogels were improved and supported cell growth and proliferation. In addition, the antibacterial properties and antioxidant activities of the EPLMA-TA hydrogels were greatly enhanced due to the addition of TA. All the findings indicate that the EPLMA-TA hydrogels with multiple properties show great potential for biomedicine applications.

Validation of the protective effects of Lonicera japonica polysaccharide on lipopolysaccharide-induced learning and memory impairments via regulation of autophagy based on network pharmacology.

BACKGROUND: Learning and memory impairments are important indexes in assessing Alzheimer's disease (AD). Lonicera japonica (L. japonica), a traditional Chinese herbal medicine, inhibits inflammation, but its role in neuroprotection is unclear. Polysaccharide is the main active ingredient in L. japonica. Here, we aimed to validate the effects of L. japonica polysaccharide (LJP) on lipopolysaccharide (LPS)-induced cognitive impairment and the underlying mechanism. METHODS: The Chinese medicine system pharmacology database and analysis platform was used to predict the target of L. japonica; the GeneCards system was used to predict the AD target. We also performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Experiments were performed after bioinformatic analysis for verification. A chronic learning and memory impairment model was established by a single administration of LPS. Learning and memory abilities of Kunming mice were examined after 7 days of induction. The protective effects of LJP on LPS-induced impairment were investigated. Neuronal damage was observed by Nissl staining. Key proteins involved in the autophagy pathway were examined. RESULTS: Bioinformatic analysis showed that there were 151 genes in the intersection of the target and ADrelated genes, and KEGG analysis suggested that these genes may act via multiple pathways. LPS-induced changes in learning and memory in mice were significantly attenuated by LJP. Nissl staining revealed that the neurons in the control group were lost and cellular arrangement was disrupted. LJP alleviated the pathological changes in the neurons of mice. The autophagy pathway was selected to verify the mechanism. ATG5, Beclin 1, Vps34, and LC3 II expression in the LPS group was significantly increased, and it was further increased in the LJP group. CONCLUSIONS: LJP improved behavioral changes and neuronal loss associated with LPS-induced learning and memory impairments. The underlying mechanism may be related to the regulation of the autophagy pathways.

Lycium barbarum Polysaccharide Inhibited Hypoxia-Inducible Factor 1 in COPD Patients.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammatory disease characterized by irreversible airflow obstruction. Pathogenic mechanisms underlying COPD remain largely unknown. Objective: The current study was designed to explore serum concentration of hypoxia-inducible factor 1α (HIF-1α) in stable COPD patients and the potential effect of Lycium barbarum polysaccharides (LBP) on HIF-1α protein expression. Methods: Serum HIF-1α was quantified by ELISA in 102 stable COPD patients before and after 2-week orally taken LBP (100 mL/time, twice daily, 5-15 mg/mL). Correlation of serum LBP and lung function (FEV1%) or blood gas (PO2 and PCO2) was also analyzed. As a control, 105 healthy subjects were also enrolled into this study. Results: Serum concentration of HIF-1α was significantly higher in the stable COPD patients (37.34 ± 7.20 pg/mL) than that in the healthy subjects (29.55 ± 9.66 pg/mL, P<0.001). Oral administration of LBP (5 mg/mL, 100 mL, twice daily for 2 weeks) not only relieved COPD symptoms but also significantly reduced serum HIF-1α concentration (36.94 ± 9.23 vs 30.49 ± 6.42 pg/mL, P<0.05). In addition, level of serum HIF-1α concentration was significantly correlated with PCO2 (r = 0.283, P<0.001), but negatively and significantly correlated with PO2 (r = -0.490, P=0.005) or FEV1%(r = -0.420, P=0.018). Conclusion: These findings suggested that activation of HIF-1 signaling pathway may be involved in the pathophysiology of COPD and that stabilization of serum HIF-1α concentration by LBP might benefit the stable COPD patients.

Preliminary analysis of serum electrolytes and body mass index in patients with and without urolithiasis.

OBJECTIVES: To compare body mass index (BMI); serum parameters; and urine parameters between patients with and without urolithiasis. METHODS: Data from 1164 patients admitted to our Department of Urology from January 2011 to July 2013 were retrospectively reviewed; 714 patients (age, 5-87 years; male:female ratio, 1.8:1) exhibited urolithiasis, and 450 patients (age, 12-94 years; male:female ratio, 3.8:1) did not. Blood and urine were collected from patients the morning after hospital admission. Serum and urine parameters were checked by an automatic biochemistry analyzer. Statistical analysis included the Mann-Whitney U test and binary logistic regression. RESULTS: Serum sodium, potassium, chloride, calcium, phosphorus, and carbon dioxide combining power significantly differed between groups. In male patients, serum sodium, calcium, and phosphorus levels were higher in the urolithiasis group, whereas serum potassium and urine pH levels were lower. In female patients, serum sodium was higher in the urolithiasis group. BMI was higher in the urolithiasis group in all patients, male and female. Respective ß-values of serum sodium and BMI in male patients were 0.077 and 0.084; in female patients, these values were 0.119 and 0.102. CONCLUSIONS: Changes in serum sodium and BMI may be involved in the pathogenesis and treatment of urolithiasis.

The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both In Vivo and In Vitro Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of Aß and Autophagy.

Chronic cerebral hypoperfusion (CCH) is closely related to the occurrence of Alzheimer's disease (AD) in the elderly. CCH can induce overactivation of autophagy, which increases the deposition of amyloid-ß (Aß) plaques in the brain, eventually impairing the cognitive function. Yuan-Zhi decoction (YZD) is a traditional Chinese medicine (TCM) formulation that is used to treat cognitive dysfunction in the elderly, but the specific mechanism is still unclear. In this study, we simulated CCH in a rat model through bilateral common carotid artery occlusion (BCCAO) and treated the animals with YZD. Standard neurological tests indicated that YZD significantly restored the impaired cognitive function after BCCAO in a dose-dependent manner. Furthermore, YZD also decreased the levels of Aß aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An in vitro model of CCH was also established by exposing primary rat hippocampal neurons to hypoxia and hypoglycemia (H-H). YZD and its active ingredients increased the survival of these neurons and decreased the levels of Aß1-40 and Aß1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both Aß aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets Aß, autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.

Dual light-induced in situ antibacterial activities of biocompatibleTiO2/MoS2/PDA/RGD nanorod arrays on titanium.

Prevention of bacterial infection and promotion of osseointegration are two important issues for titanium (Ti) implants in medical research. In addition, after a biofilm is formed on the surface of implants, the immune system and antibiotic therapy may fail. In this work, bio-functionalized titanium dioxide (TiO2)/molybdenum disulfide (MoS2)/polydopamine (PDA)/arginine-glycine-aspartic acid (RGD) nanorod arrays (NAs) are prepared on Ti implants to not only kill bacteria noninvasively upon co-irradiation of 660 nm visible light (VL) and 808 nm near infrared (NIR) light, but also promote the osteogenic activity simultaneously. Dual light irradiation triggers the TiO2/MoS2 NA to generate hyperthermia and reactive oxygen species (ROS) in 10 min. The synergistic effects of the generated hyperthermia and ROS increase the bacterial membrane permeability and bacteria are killed rapidly and efficiently in vitro and in vivo. The biofilm is also eradicated and RGD on the nanorods improves cell adhesion, proliferation, and osteogenic differentiation. The strategy described here for the design of bio-functionalized coatings on Ti implants has great clinical potential in orthopedics, dentistry, and other medical fields.

Functional diversity drives ecosystem multifunctionality in a Pinus yunnanensis natural secondary forest.

It is essential to understand how the loss of biodiversity impacts both ecosystem function (EF) and multifunctionality (EMF). Previous studies have mostly focused on predicting how species richness (SR) impacts EMF, while the effect of functional diversity (FD) on EMF remains unclear. Specifically, we know little about the primary functional drivers impacting EMF compared with SR. Therefore, we analysed 8 ecosystem functions within 58 natural secondary forest plots to investigate the effect of FD on both individual EF and EMF. Our results suggest that SR and FD had very significant positive effects on plant phosphorus, soil available phosphorus, and soil total nitrogen. FD explained significantly more variations in these functional responses than SR for individual ecosystem functioning. We also used a multiple threshold approach to test the effect of SR and FD on EMF. We found that FD and SR were positively related to EMF regardless of whether low-level function or high-level function was desired, but FD had a larger effect than SR. Based on the averaging approach, OLS regression, multivariate linear regression model and random forest analysis, we found that SR and FD were both drivers of EMF but that FD had a stronger effect and could explain more variation. As such, we conclude that FD drives ecosystem multifunctionality more than SR.

Chinese Herbal Complex 'Bu Shen Jie Du Fang' (BSJDF) Modulated Autophagy in an MPP+-Induced Cell Model of Parkinson's Disease.

Autophagy plays an important role in the development of Parkinson disease (PD). Previous studies showed that autophagy could protect cells from α-synuclein toxicity and promote functional coupling of mitochondria. But it is still a question whether modulating autophagy can be used to treat PD. In traditional Chinese medicine, a specific Chinese herbal complex called Bu Shen Jie Du Fang (BSJDF) has a long history of treating motor impairments similar to Parkinson disease, while its mechanism is still unclear. As a pilot study, we aimed to evaluate the efficacy and its mechanism of Bu Shen Jie Du Fang in an MPP+-induced cell model of Parkinson's disease. And the phase contrast microscope (PCM) revealed that the BSJDF group had the greatest surviving cell counts compared with all other treated cell groups except the normal group. And Cell Counting Kit 8 (CCK8) assays showed a similar result. In BSJDF group, 3.7 ×107 cells/dish was identified by hemocytometer counts, which was significantly higher than other groups except the normal cells (p<0.05). In the BSJDF group, autophagy can be observed by transmission electron microscopy (TEM). Protein expression of Atg12 and LC3 in the BSJDF group was upregulated compared to the PD model group (p<0.05). Atg12 mRNA expression was also upregulated in the BSJDF group (p<0.05). In conclusion, our study indicated that the therapeutic mechanisms of BSJDF may be mediated by stimulating autophagy, and modulating autophagy can be used to treat PD.

Neuroprotective effects of tenuigenin on neurobehavior, oxidative stress, and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats.

BACKGROUND: Tenuigenin (TEN), a major active component of the Chinese herb Polygala tenuifolia root, has been used to improve memory and cognitive function in Traditional Chinese Medicine for centuries. PURPOSE: The present study was designed to explore the possible neuroprotective effect of TEN on the streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD). METHODS: STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8 mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors were evaluated using the Morris water maze test. Hyperphosphorylation of tau proteins in hippocampus were measured by western blot assay. Superoxide dismutase activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal adducts contents were also measured in the hippocampus. RESULTS: Treatment with TEN significantly improved STZ-induced cognitive damage, markedly reduced changes in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited STZ-induced reduction in superoxide dismutase and glutathione peroxidase activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl staining results showed that TEN has protective effects on hippocampal neurons. CONCLUSION: These results provide experimental evidence demonstrating preventive effect of TEN on cognitive dysfunction, oxidative stress, and hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may have beneficial effects in the treatment of neurodegenerative disorders such as AD.

Galactose-1-phosphate uridyltransferase (GalT), an in vivo-induced antigen of Actinobacillus pleuropneumoniae serovar 5b strain L20, provided immunoprotection against serovar 1 strain MS71.

GALT is an important antigen of Actinobacillus pleuropneumoniae (APP), which was shown to provide partial protection against APP infection in a previous study in our lab. The main purpose of the present study is to investigate GALT induced cross-protection between different APP serotypes and elucidate key mechanisms of the immune response to GALT antigenic stimulation. Bioinformatic analysis demonstrated that galT is a highly conserved gene in APP, widely distributed across multiple pathogenic strains. Homologies between any two strains ranges from 78.9% to 100% regarding the galT locus. Indirect enzyme-linked immunosorbent assay (ELISA) confirmed that GALT specific antibodies could not be induced by inactivated APP L20 or MS71 whole cell bacterin preparations. A recombinant fusion GALT protein derived from APP L20, however has proven to be an effective cross-protective antigen against APP sevorar 1 MS71 (50%, 4/8) and APP sevorar 5b L20 (75%, 6/8). Histopathological examinations have confirmed that recombinant GALT vaccinated animals showed less severe pathological signs in lung tissues than negative controls after APP challenge. Immunohistochemical (IHC) analysis indicated that the infiltration of neutrophils in the negative group is significantly increased compared with that in the normal control (P<0.001) and that in surviving animals is decreased compared to the negative group. Anti-GALT antibodies were shown to mediate phagocytosis of neutrophils. After interaction with anti-GALT antibodies, survival rate of APP challenged vaccinated animals was significantly reduced (P<0.001). This study demonstrated that GALT is an effective cross-protective antigen, which could be used as a potential vaccine candidate against multiple APP serotypes.

Effects of dietary live yeast supplementation on growth performance, diarrhoea severity, intestinal permeability and immunological parameters of weaned piglets challenged with enterotoxigenic Escherichia coli K88.

This study aimed to investigate the effects of dietary live yeast (LY) supplementation on growth, intestinal permeability and immunological parameters of piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Piglets weaned at 21 d were allocated into three treatments with six pens and six piglets per pen, receiving the control diet (CON), diets supplemented with antibiotics plus zinc oxide (ANT-ZnO) and LY (Saccharomyces cerevisiae strain CNCM I-4407), respectively, for a period of 2 weeks. On day 8, thirty-six piglets were selected as control without ETEC (CON), CON-ETEC, ANT-ZnO-ETEC and LY-ETEC groups challenged with ETEC until day 10 for sample collections. Piglets fed ANT-ZnO diet had the highest average daily gain and average daily feed intake (P<0·05) during the 1st week, but ADG of piglets fed the ANT-ZnO diet was similar as piglets fed LY diet during the second week. Piglets with LY-ETEC or ANT-ZnO-ETEC had markedly lower diarrhoea score (P<0·05) than piglets with CON-ETEC during the 24 h after ETEC challenge. Relative to piglets with CON, the counts of E. coli, urinary ratio of lactulose to mannitol, plasma IL-6 concentration, mRNA abundances of innate immunity-related genes in ileum and mesenteric lymph node tissues were increased (P<0·05), whereas the villous height of jejunum and relative protein expression of ileum claudin-1 were decreased (P<0·05) in piglets with CON-ETEC; however, these parameters did not markedly change in piglets with LY-ETEC or ANT-ZnO-ETEC. In summary, dietary LY supplementation could alleviate the severity of diarrhoea in piglets with ETEC, which may be associated with the improved permeability, innate immunity and bacterial profile.

Herbal Medicine Cordyceps sinensis Improves Health-Related Quality of Life in Moderate-to-Severe Asthma.

Moderate-to-severe asthma has a substantial impact on the health-related quality of life (HR-QOL) of the patients. Cordyceps sinensis is a traditional Chinese medicine that is evaluated clinically for the treatment of many diseases, such as chronic allograft nephropathy, diabetic kidney disease, and lung fibrosis. In order to investigate the effects of Cordyceps sinensis on patients with moderate-to-severe persistent asthma, 120 subjects were randomized to receive Corbin capsule containing Cordyceps sinensis for 3 months (treatment group, n = 60), whereas the control group (n = 60) did not receive treatment with Corbin capsule. Inhaled corticosteroid and as-needed ß-agonists were used in the treatment of both groups. HR-QOL was measured with the Juniper's Asthma Quality of Life Questionnaire (AQLQ). The incidence of asthma exacerbation, pulmonary function testing, and serum measurements of inflammatory mediators were also evaluated. The results showed that the treatment group indicated a significant increase in AQLQ scores and lung function compared with the control group. The expression levels of the inflammation markers IgE, ICAM-1, IL-4, and MMP-9 in the serum were decreased and IgG increased in the treatment group compared with the control group. Therefore, the conclusion was reached that a formulation of Cordyceps sinensis improved the HR-QOL, asthma symptoms, lung function, and inflammatory profile of the patients with moderate-to-severe asthma. This trial is registered with ChiCTR-IPC-16008730.