High altitude retinopathy: An overview and new insights.

High altitude retinopathy (HAR) is a common ocular disorder that occurs on ascent to high altitude. There are many clinical symptoms, retinal vascular dilatation, retinal edema and hemorrhage are common. These usually do not or slightly affect vision; rarely, severe cases develop serious or permanent vision loss. At present, the research progress of HAR mainly focuses on hemodynamic changes, blood-retinal barrier damage, oxidative stress and inflammatory response. Although the related studies on HAR are limited, it shows that HAR still belongs to hypoxia, and hypobaric hypoxia plays an aggravating role in promoting the development of the disease. Various studies have demonstrated the correlation of HAR with acute mountain sickness (AMS) and high-altitude cerebral edema (HACE), so a deeper understanding of HAR is important. The slow ascent rates and ascent altitude are the key to preventing any altitude sickness. Research on traditional chinese medicine (TCM) and western medicine has been gradually carried out. Further exploration of the pathogenesis and prevention strategies of HAR will provide better guidance for doctors and high-altitude travelers.

Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability.

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 µmol·L-1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100-150 mg·kg bw-1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

A Novel Preparation Method for Effervescent Tablets of Xianganfang Containing Fresh Juice using a Semi-Solid Extrusion 3D Printer with Three Cartridge Holders.

This study aimed to prepare effervescent tablets of traditional Chinese medicine Xianganfang with fresh juice using a semi-solid 3D printer with three cartridge holders to seperate acid and alkali source by drug paste through model design to avoid sticking impact and premature effervescence during the tableting in the conventional preparation process. The powder of Xianganfang including fresh juice of Phyllanthus emblica and licorice extract was obtained by vacuum freeze-drying with 50% mannitol as cryoprotectant. Then, the formulation of 3D-printed effervescent tablets was investigated. Further 5% HPMC hydroalcoholic gel was mixed with sodium bicarbonate and freeze-dried Xianganfang powder to prepare alkali source and drug paste respectively while 30% PVP ethanol solution was mixed with tartaric acid to prepare acid source paste; these three pastes had good printability. The pastes of drug, acid, and alkali were loaded into three syringe cartridges separately and numbered as "3," "5," and "7," according to cartridge holders of the 3D printer, and printed in the order of "537,353,735" for separating acid and alkali by drug to avoid premature effervescence. And the basic printing parameters were optimized. The tablets were evaluated by the appearance, tablet weight variation, hardness, disintegration time, friability, pH, and stability. The physicochemical properties all conformed to the Chinese Pharmacopoeia 2020 edition. The content of the active ingredient gallic acid was 0.769 ± 0.019 mg/g. This study provided a new method to prepare effervescent tablets of traditional Chinese medicine with fresh juice using 3D printing technology.

Evaluation of the antimicrobial and cytotoxic potential of endophytic fungi extracts from mangrove plants Rhizophora stylosa and R. mucronata.

Mangrove endophytic fungi are tolerant to numerous stresses and are inevitably capable of exhibiting excellent biological activity by producing impressive numbers of metabolites with special biological functions, based on previous work on the biological potential of mangrove-derived endophytic fungi. To obtain marked antimicrobial and cytotoxic fermentation products of culturable endophytic fungi from mangrove forests, our research evaluated the antimicrobial and cytotoxic activities of crude extracts of endophytic fungi from Rhizophora stylosa and Rhizophora mucronata. Forty-six fungal isolates were cultured on four different media, namely, dextrose agar (PDA), Czapek's agar (CZA), rice medium (RM) and grain medium (GM) and harvested by ethyl acetate solvent at 40 days. The extracts were tested for antimicrobial activity by the microdilution method against the gram-negative bacteria Pseudomonas adaceae (PA), gram-positive bacteria Enterococcus faecalis (EF), methicillin-resistant Staphylococcus aureus (MRSA) and pathogenic fungus Monilia albicans (MA). The cytotoxic activity of the extracts was evaluated by MTT assay using A549 human lung cancer cells, HeLa human cervical carcinoma cells, and HepG2 human hepatocellular cells. The results showed that rice medium could promote the secretion of antimicrobial and antitumour secondary metabolites of endophytic fungi in comparison with other cultivation media. Seventeen strains (68%) from R. stylosa exhibited inhibitory effects on indicators, especially N. protearum HHL46, which could inhibit the growth of four microbes with MIC values reaching 0.0625 mg/mL. Fifteen strains (71.4%) from R. mucronata displayed activities against human pathogenic microbes; in particular, Pestalotiopsis sp. HQD6 and N. protearum HQD5 could resist the growth of four microbes with MIC values ranging from 0.015 to 1 mg/mL. In the cytotoxicity assay, the extracts of 10 strains (40%), 9 strains (40%) and 13 strains (52%) of R. stylosa and 13 strains (61.9%), 10 strains (47.6%) and 10 strains (47.6%) of R. mucronata displayed cytotoxicity against A549, HeLa and HepG2 cancer cells with cell viability values ≤ 50%. Neopestalotiopsis protearum HHL46, Phomopsis longicolla HHL50, Botryosphaeria fusispora HQD83, Fusarium verticillioides HQD48 and Pestalotiopsis sp. HQD6 displayed significant antitumour activity with IC50 values below 20 µg/mL. These results highlighted the antimicrobial and antitumour potential of endophytic fungi from R. stylosa and R. mucronata and the possibility of exploiting their antimicrobial and cytotoxic agents.

Chemical epigenetic modifiers enhance the production of immunosuppressants from the endophytic fungus Aspergillus fumigatus isolated from Cynodon dactylon.

Chemical epigenetic modifiers applied on a plant endophytic fungus Aspergillus fumigatus isolated from a healthy stem of terrestrial plant Cynodon dactylon, significantly changed of metabolic profile and resulted in the isolation of nineteen compounds, including ten alkaloids (1-10), six polyketides (11-16), and three benzene derivatives (17-19). This is the first report of 14, 18 and 19 being isolated from this fungal species. And compound 14 was known as a synthetic product and isolated as a natural product for the first time. HPLC profiles of the control and treated samples indicated that compounds 11, 16, 18 are belonged to the newly induced secondary metabolites. Their structures were elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated.

Effect of Dihydropyridine Enrichment in the Microstructure of the Palisade Layer on the Stability of Fat Nano-emulsions.

Relationship between the stability of fat nano-emulsions and the incorporated drug at the molecular level are rarely known. Herein, fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0 mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton nuclear magnetic resonance (1H NMR) signal intensity of the lecithin trimethyl ammonium group in the nimodipine and felodipine nano-emulsions. The 1H NMR spectra of test solutions including nano-emulsions suggest that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75 mg/mL, and 0.30 and 0.90 mg/mL respectively, which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are positively correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validate the effect of drugs on the arrangement of lecithin in the palisade layer. 1H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.

Warpage optimization and influence factors analysis of 3D printing personalized JJY tablets.

To explore the feasibility of preparing traditional Chinese medicine using 3 D printing technology and reduce warpage commonly occurs in large-size tablets, we investigated the prescription, warpage optimization and influence factors of 3 D printing Jiuxiang Jianpi Yangwei (JJY) tablets. The procedures used conformed to the requirements of the 2015 edition of the Chinese Pharmacopeia. The results of the prescription screening showed that 75% ethanol and HPMC (9%) could be adhesives. Meanwhile, stevia (0.5%) and citric acid (0.5%) improved the taste of the 3 D printed JJY tablets. To ensure the quality and appearance of the printed tablets, the best parameters were as follows: drying at room temperature, 40% of the filling density, a 3 mm model height, two outer ring numbers and a printing speed of 15 mm/s. The optimized printed tablets had a smooth appearance, suitable hardness, with the weight uniformity in accordance with the Pharmacopeia. We also prepared personalized JJY cartoon tablets (which contained images of a big-headed pig and a small yellow duck) which were designed to increase the compliance of children when taking their medications. In conclusion, this study reported that 3 D printing technology has great potential for preparing traditional Chinese medicines, and it provided guidance for 3 D printing tablets without warpage.

Protective effects of grape seed proanthocyanidins against iron overload-induced renal oxidative damage in rats.

BACKGROUND: Excessive exposure to iron can cause kidney damage, and chelating drugs such as deferoxamine and deferiprone have limited usefulness in treating iron poisoning. This study was designed to investigate the protective effects of grape seed proanthocyanidins (GSPAs) against iron overload induced nephrotoxicity in rats. The roles of GSPAs in chelating iron, antioxidant activity, renal function, pathological section, and apoptosis-related gene expression were assessed. METHODS: Newly weaned male Sprague-Dawley rats aged 21 days (weight, 65 ±â€¯5 g) were randomly divided into four groups containing 10 rats each: normal control (negative) group, iron overload (positive) group, GSPAs group, and GSPAs + iron overload (test) group. Iron dextran injections (2.5 mg⋅ kg-1) and GSPAs (25 mg⋅ kg-1) were intraperitoneally and intragastrically administered to rats daily for 7 weeks, respectively. Measurements included red blood cell (RBC) count and hemoglobin (Hb) level, serum total iron-binding capacity (TIBC), renal iron content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, total antioxidant activity (T-AOC), creatinine (CR) and blood urea nitrogen (BUN) levels, pathological changes, and apoptotic Fas, Bax expressions in the kidney tissue. Differences among the dietary groups were determined using one-way analysis of variance with post-hoc Tukey's test. P < 0.05 was considered statistically significant. RESULTS: RBC count, Hb level, renal iron content, MDA content, CR and BUN levels, and Fas, Bax expressions significantly increased in the positive group than in the negative group; contrarily, TIBC, GSH-Px activity, and T-AOC significantly decreased in the positive group than in the negative group (P < 0.05). Although not statistically significant, SOD activity was slightly reduced in the positive group than in the negative group. Inflammatory cell infiltration and fibrous tissue proliferation were observed in the kidney tissue of the rats in the positive group; in contrast, the rats exhibited better recovery when GSPAs were used instead of iron alone. Compared with the positive group, RBC counts, Hb levels, renal iron contents, the MDA content, CR and BUN levels, and Fas, Bax expressions significantly decreased, whereas the TIBC, the GSH-Px and SOD activities as well as T-AOC significantly increased in the test group rats (P < 0.05). There were no significant differences in the RBC counts, Hb levels, TIBC, renal iron contents, the SOD activity and MDA content, CR and BUN levels, and Fas expression between the GSPAs and negative groups. The GSH-Px activity and T-AOC were significantly increased whereas Bax expression was significantly decreased in the GSPAs group rats than in the negative group rats (P < 0.05). The rats in the GSPAs, test, and negative groups displayed glomeruli and tubules with a clear structure; further, the epithelial cells in the renal tubules were neatly arranged. CONCLUSIONS: GSPAs have protective effects on nephrotoxicity in rats with iron overload. Thus, further investigation of GSPAs as a new and natural phytochemo-preventive agent against iron overload is warranted.

Alleviation Effect of Grape Seed Proanthocyanidins on Neuronal Apoptosis in Rats with Iron Overload.

We aimed to evaluate the effect of grape seed proanthocyanidins (GSPCs) on neuronal apoptosis, particularly through their roles in maintaining divalent mineral element balance and resisting oxidation in rats with iron overload. A total of 40 Sprague-Dawley rats were randomly divided into control, iron overload, GSPCs, and iron overload + GSPCs groups. The iron, calcium, zinc, magnesium, and copper contents in the brain tissue of the rats were measured using inductively coupled plasma mass spectrometry. Their oxidative stress state was determined using the relevant kit. The number of apoptotic neurons was evaluated using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and synaptosome numbers were determined using the immunohistochemical approach. Fas, Bax, and Bcl-2 gene expressions in the cortex and hippocampus were detected using quantitative real-time polymerase chain reaction. After 7 weeks, compared with the control group, the zinc and magnesium contents; superoxide dismutase, glutathione peroxidase, and catalase activities; and synaptophysin and Bcl-2 gene expressions in the iron overload group were significantly decreased, whereas the iron, calcium contents, and malondialdehyde contents; TUNEL-positive cell numbers; and Fas and Bax gene expressions were significantly increased. There were no significant changes in the copper content. Conversely, the rats exhibited better recovery when GSPCs were used instead of iron alone. In summary, GSPCs protected against iron overload induced neuronal apoptosis in rats by maintaining the divalent mineral element balance, reducing oxidative stress, and regulating apoptotic genes expressions.

Efficacy of Purtscher's Retinopathy Treatments: A Systematic Review.

OBJECTIVE: The aim of this review is to evaluate the efficacy of available Purtscher's Retinopathy treatments. MATERIALS AND METHODS: In order to collect single-case reports, electronic searches were conducted in several databases including PubMed, Embase, Web of Science, China National Knowledge Infrastructure, SinoMed, VIP, and WanFang in the Electronic Theses and Dissertations Center. In VIP and Wanfang, we also traced the references of included articles. Risk of bias was evaluated using a tool adapted from the Cochrane Risk of Bias Tool. Statistical analysis was done in SPSS19.0. Evidence was evaluated and graded with GRADE system. RESULTS: In total, 76 studies were included involving 88 cases and 139 eyes. Serious bias existed in 90% of the included studies. Current treatments for Purtscher's retinopathy included glucocorticoid therapy (63.29%), traditional Chinese medicine therapy (10.13%), glucocorticoid integrative medicine therapy (7.60%), and integrative medicine therapy (6.33%). Patients' eyesight with (56.83%) or without (43.17%) treatment both improved in the follow-up within 1-3 months, 4-6 months, and more than 6 months; however, conditions without treatment became better compared to the treatment groups in after 4-6 months and more than 6 months. All results were "very low" in the GRADE system. None of the studies reported adverse reactions in any patient. CONCLUSIONS: Both treatment and no treatment improve vision in Purtscher's retinopathy patients, but the difference between no treatment and glucocorticoid therapy had no statistical significance. The evidence quality for this conclusion was "very low" and had large bias. Further research is required to understand the safety of Purtscher's retinopathy treatment.

Chemical characterization, anti-benign prostatic hyperplasia effect and subchronic toxicity study of total flavonoid extract of Pteris multifida.

The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia.