The feasibility of using pathobiome strains as live biotherapeutic products for human use.

The evaluation of pathobiome strains should be conducted at the strain level, involving the identification of the functional genes, while considering the impact of ecological niche and drug interactions. The safety, efficacy, and quality management of live biotherapeutic products (LBPs), especially pathobiome strains, have certain peculiarities. Promising development methods include the recombinant LBP and active metabolites.

A case report of chronic dacryocystitis caused by nasal stones.

BACKGROUND: This paper reports a case of chronic dacryocystitis due to nasal stones. CASE PRESENTATION: An 84-year-old male patient was admitted to the hospital with chronic dacryocystitis of the right eye due to tearing and purulent discharge from the right eye for more than 1 month. Antibiotic treatments such as gatifloxacin eye drops were given at other hospitals but did not relieve the symptoms. A computed tomography(CT) scan of the lacrimal duct in our department showed a high-density shadow in the right lacrimal sac area, hypertrophy of the right inferior turbinate, and many nasal calculi in the nasal cavity. The patient was transferred to our otolaryngology department for further treatment, and nasal stones were removed under nasal endoscopy. Three days after surgery, the symptoms affecting the patient's right eye gradually resolved. One month after surgery, the patient underwent a follow-up examination in the ophthalmology clinic; there was no lacrimal purulent discharge from the right eye, and the lacrimal duct could be flushed smoothly. CONCLUSION: Chronic dacryocystitis is often caused by primary nasolacrimal duct obstruction. Cases of chronic dacryocystitis caused by secondary nasolacrimal duct obstruction due to nasal stones are rare in the clinic. This case can serve as a reference for the clinical diagnosis and treatment of chronic dacryocystitis.

Generic Reversible Visible Watermarking via Regularized Graph Fourier Transform Coding.

Reversible visible watermarking (RVW) is an active copyright protection mechanism. It not only transparently superimposes copyright patterns on specific positions of digital images or video frames to declare the copyright ownership information, but also completely erases the visible watermark image and thus enables restoring the original host image without any distortion. However, existing RVW algorithms mostly construct the reversible mapping mechanism for a specific visible watermarking scheme, which is not versatile. Hence, we propose a generic RVW framework to accommodate various visible watermarking schemes. In particular, we obtain a reconstruction data packet-the compressed difference image between the watermarked image and the original host image, which is embedded into the watermarked image via any conventional reversible data hiding method to facilitate the blind recovery of the host image. The key is to achieve compact compression of the difference image for efficient embedding of the reconstruction data packet. To this end, we propose regularized Graph Fourier Transform (GFT) coding, where the difference image is smoothed via the graph Laplacian regularizer for more efficient compression and then encoded by multi-resolution GFTs in an approximately optimal manner. Experimental results show that the proposed framework has much better versatility than state-of-the-art methods. Due to the small amount of auxiliary information to be embedded, the visual quality of the watermarked image is also higher.

Salvianolic acid A increases the accumulation of doxorubicin in brain tumors through Caveolae endocytosis.

Brain glioma is one of the most common brain tumors in the central nervous system (CNS). The blood-brain tumor barrier (BTB) restricts the delivery of anti-tumor drugs into tumor tissue in the brain. Therefore, improving the transportation of antineoplastic drugs across the BTB is essential to ameliorate treatment of brain tumors. The present study was performed to explore the effect and mechanism of salvianolic acid A (Sal A) on transportation of doxorubicin (Dox) across the BTB in vivo and in vitro. By creating a brain C6 glioma model in rats, we demonstrated that Sal A significantly increased the level of Dox in brain tumor tissue as shown by liquid chromatograph mass spectrometry. Interestingly, we found that Sal A increased transendothelial electrical resistance (TEER) values of the BTB and decreased the permeability of FITC-Dextran (4kD) across the BTB in vitro. Furthermore, the expression of tight junction proteins (TJs) in glioma endothelial cells (GECs) and brain tumor microvessels were also increased, suggesting that Sal A enhanced delivery of Dox across the BTB independent of the paracellular pathway. Next, we detected that Sal A had an effect on transcellular transport of compounds across the BTB. The accumulation of FITC-labeled bovine serum albumin (FITC-BSA) was significantly increased in GECs after treatment with Sal A (10 µM) for 6h, which was inhibited after pre-treatment with methyl-ß-cyclodextrin (MßCD) for 30 min. The increased delivery of Dox across the BTB was also reduced after treatment with MßCD. In addition, phosphorylation levels of protein kinase B (PKB) and tyrosine protein kinase-Src family (Src) were increased in the Sal A treatment group. Sal A up-regulated the expression level of the phosphorylation of Caveolin-1 (pCaveolin-1), and this effect was reversed by a PKB or Src inhibitor. Taken together, our study showed for the first time that Sal A facilitated the delivery of antitumor drugs into brain tumor tissues by targeting the PKB/Src/Caveolin-1 signaling pathway.

A new oleanane type pentacyclic triterpenoid saponin from the husks of xanthoceras sorbifolium bunge and its neuroprotection on PC12 cells injury induced by Aß25-35.

A new triterpenoid saponin (1), 3-O-[ß-D-glucopyranosyl(1→6)]-(2'-angeloyl)-ß-D-glucopyranosyl-28-O-ß-D-glucopyranosyl(1→6)[α-L-rhamnopyranosyl(1→2)-ß-D-glucopyranosyl]-21-O-acetyl-16-deoxybarringtogenol C, together with four known saponins (2 ∼ 5) were isolated from the husks of Xanthoceras sorbifolium Bunge. Their structures were characterized by HR-ESI-MS, 1D-NMR, 2D-NMR spectra and chemical methods. Compound 1 exhibited excellent neuroprotection on PC12 cells injury induced by Aß25-35 at the doses of 150 µmol/L and 200 µmol/L. The cell viabilities were (76.18 ± 2.09) % and (76.02 ± 3.20) %, respectively.[Formula: see text].

Metabolomics analysis of Xanthoceras sorbifolia husks protection of rats against Alzheimer's disease using liquid chromatography mass spectrometry.

The promising effect of Xanthoceras sorbifolia Bunge husks against Alzheimer's disease has attracted more and more attention; however, its therapeutic mechanism has been unclear. A metabolomics study of the husks on rat serum and brain was carried out. Cognitive impairment of rats was induced by D-galactose and amyloid ß, and the result was evaluated by Morris water maze test and brain histological analysis. The metabolite profiling was performed through ultra-high-performance liquid chromatography time-of-flight mass spectrometry. Twelve potential biomarkers were identified in the rat serum and nineteen in the brain. All the biomarkers could be classified as amino acids, lipids, purines and bile acids. Both the husk extract and control drug, huperzine A, showed protective effect against the cognitive disorder induced by amyloid ß, however, the husk extract exhibited significant effect on more targets, which included arachidonic acid, cholic acid, uric acid and citric acid etc., indicating the regulation of the husks of more pathways including neuroinflammation, energy metabolism and antioxidant ability. Triterpenoid saponins and polyphenols in the husks may contribute to the regulation of these pathways. This comprehensive study revealed the underlying therapeutic mechanism of the husks against Alzheimer's disease; some potential biomarkers for its clinical diagnosis were also provided.

Classic Prescription, Kai-Xin-San, Ameliorates Alzheimer's Disease as an Effective Multitarget Treatment: From Neurotransmitter to Protein Signaling Pathway.

Alzheimer's disease (AD) is a widespread neurodegenerative disease caused by complicated disease-causing factors. Unsatisfactorily, curative effects of approved anti-AD drugs were not good enough due to their actions on single-target, which led to desperate requirements for more effective drug therapies involved in multiple pathomechanisms of AD. The anti-AD effect with multiple action targets of Kai-Xin-San (KXS), a classic prescription initially recorded in Bei Ji Qian Jin Yao Fang and applied in the treatment of dementia for thousands of years, was deciphered with modern biological methods in our study. Aß 25-35 and D-gal-induced AD rats and Aß 25-35-induced PC12 cells were applied to establish AD models. KXS could significantly improve cognition impairment by decreasing neurotransmitter loss and enhancing the expression of PI3K/Akt. For the first time, KXS was confirmed to improve the expression of PI3K/Akt by neurotransmitter 5-HT. Thereinto, PI3K/Akt could further inhibit Tau hyperphosphorylation as well as the apoptosis induced by oxidative stress and neuroinflammation. Moreover, all above-mentioned effects were verified and blocked by PI3K inhibitor, LY294002, in Aß 25-35-induced PC12 cells, suggesting the precise regulative role of KXS in the PI3K/Akt pathway. The utilization and mechanism elaboration of KXS have been proposed and dissected in the combination of animal, molecular, and protein strategies. Our results demonstrated that KXS could ameliorate AD by regulating neurotransmitter and PI3K/Akt signal pathway as an effective multitarget treatment so that the potential value of this classic prescription could be explored from a novel perspective.

Study on the Multitarget Synergistic Effects of Kai-Xin-San against Alzheimer's Disease Based on Systems Biology.

Kai-Xin-San (KXS), a classical Chinese traditional prescription, was widely applied in the treatment of Alzheimer's disease (AD), while its functional mechanisms still remain unclear. By using systems biology approaches at animal, cellular, and molecular levels, the improvement of KXS on cognitive impairment was achieved by inhibiting abnormal acetylcholinesterase. The function on the nerve skeleton was performed by regulating the Tau phosphorylation pathway. Its antioxidant, anti-inflammatory, and antiapoptotic effects by modulating the aberrant upregulation of ROS, proinflammatory factors, and apoptosis-related proteins in the brain were studied to reveal the synergistic therapeutic efficacy of KXS. Then, formula dismantling in vitro indicated that ginseng was the principal herb, whereas three other herbs served adjuvant roles to achieve the best effect. After that, the in vivo analysis of components into plasma and brain of AD rats showed that 8 of 23 components in blood and 4 of 10 components in brain were from ginseng, respectively, further verifying the principal status of ginseng and the synergistic effects of the formula. Thus, the anti-AD effects of KXS were achieved by multitargets and multichannels. The systems biology approaches presented here provide a novel way in traditional herbal medicine research.

Integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques for the metabolic profiling of Xanthoceras sorbifolia Bunge husks in rat plasma, urine, and feces.

An integrated strategy based on high-resolution mass spectrometry coupled with multiple data mining techniques was developed to screen the metabolites in rat biological fluids after the oral administration of Xanthoceras sorbifolia Bunge husks. Mass defect filtering, product ion filtering, and neutral loss filtering were applied to detect metabolites from the complex matrix. As a result, 55 metabolites were tentatively identified, among which 45 barrigenol-type triterpenoid metabolites were detected in the feces, and six flavonoids and four coumarins metabolites were in the urine. Moreover, eight prototype constituents in plasma, 36 in urine and 23 in feces were also discovered. Due to the poor bioavailability of barrigenol type triterpenoids, most of them were metabolized by intestinal flora. Phase I metabolic reactions such as deglycosylation, oxidation, demethylation, dehydrogenation, and internal hydrolysis were supposed to be their principal metabolic pathways. Coumarins were found in all the biosamples, whereas flavonoids were mainly in the urine. Unlike the saponins, they were mainly metabolized through phase II metabolic reactions like glucuronidation and sulfonation, which made them eliminated more easily by urine. This work suggested the metabolic profile of X. sorbifolia husks for the first time, which will be very valuable for its further development.

A time-of-flight mass spectrometry based strategy to fast screen triterpenoids in Xanthoceras sorbifolia Bunge husks for bioactive substances against Alzheimer's disease.

Xanthoceras sorbifolia Bunge is a folk medicine in China. Recently, the triterpenoids in its husks have attracted more and more attention for potential prevention against Alzheimer's disease. However, current studies on its bioactive substances were still insufficient. To reveal more bioactive substances, an efficient and practical strategy based on high resolution mass spectra coupled with multiple data mining techniques was developed to characterize the barrigenol type triterpenoids in the husks and dosed rat plasma. A total of 50 barrigenol type triterpenoids were identified in the husks, and 6 of these were detected in the rat plasma, which were regarded as bioactive candidates. To find the real bioactive substances, the neuroprotective effect of the candidates was further tested by calculating the PC12 cell viability against amyloid-ß-induced cytotoxicity. As a result, three out of the six candidates exhibited obvious neuroprotction against amyloid-ß-induced cytotoxicity on PC12 cells, indicating their potential to be bioactive substances against Alzheimer's disease. This study will be a valuable reference of the bioactive substances in Xanthoceras sorbifolia Bunge husks against Alzheimer's disease and the provided strategy can also be applied to the exploration of the effective constituents in other medicines.