Curcumol: a review of its pharmacology, pharmacokinetics, drug delivery systems, structure-activity relationships, and potential applications.

Curcumol (Cur), a guaiane-type sesquiterpenoid hemiketal, is an important and representative bioactive component extracted from the essential oil of the rhizomes of Curcumae rhizoma which is also known as "Ezhu" in traditional Chinese medicine. Recently, Cur has received considerable attention from the research community due to its favorable pharmacological activities, including anti-cancer, hepatoprotective, anti-inflammatory, anti-viral, anti-convulsant, and other activities, and has also exerted therapeutic effect on various cancers, liver diseases, inflammatory diseases, and infectious diseases. Pharmacokinetic studies have shown that Cur is rapidly distributed in almost all organs of rats after intragastric administration with high concentrations in the small intestine and colon. Several studies focusing on structure-activity relationship (SAR) of Cur have shown that some Cur derivatives, chemically modified at C-8 or C-14, exhibited more potent anti-cancer activity and lower toxicity than Cur itself. This review aims to comprehensively summarize the latest advances in the pharmacological and pharmacokinetic properties of Cur in the last decade with a focus on its anti-cancer and hepatoprotective potentials, as well as the research progress in drug delivery system and potential applications of Cur to date, to provide researchers with the latest information, to highlighted the limitations of relevant research at the current stage and the aspects that should be addressed in future research. Our results indicate that Cur and its derivatives could serve as potential novel agents for the treatment of a variety of diseases, particularly cancer and liver diseases.

Dissection of transcriptome and metabolome insights into the isoquinoline alkaloid biosynthesis during stem development in Phellodendron amurense (Rupr.).

Phellodendron amurense (Rupr.) is a well-known medicinal plant with high medicinal value, and its various tissues are enriched in various active pharmaceutical ingredients. Isoquinoline alkaloids are the primary medicinal component of P. amurense and have multiple effects, such as anti-inflammation, antihypertension, and antitumor effects. However, the potential regulatory mechanism of isoquinoline alkaloid biosynthesis during stem development in P. amurense is still poorly understood. In the present study, a total of eight plant hormones for each stem development stage were detected; of those, auxin, gibberellins and brassinosteroids were significantly highly increased in perennial stems and played key roles during stem development in P. amurense. We also investigated the content and change pattern of secondary metabolites and comprehensively identified some key structural genes involved in the isoquinoline alkaloid biosynthesis pathway by combining the transcriptome and metabolomics. A total of 39,978 DEGs were identified in the present study, and six of those had candidate structural genes (NCS, GOT2, TYNA, CODM, TYR, TAT and PSOMT1) that were specifically related to isoquinoline alkaloid biosynthesis in P. amurense. Corydalmine, cyclanoline, dehydroyanhunine, (S)-canadine and corybulbine were the most significantly upregulated metabolites among the different comparative groups. Three differentially expressed metabolites, dopamine, (S)-corytuberine and (S)-canadine, were enriched in the isoquinoline alkaloid biosynthesis pathway. Furthermore, bHLH and WRKY transcription factors play key roles in the isoquinoline alkaloid biosynthesis pathway in P. amurense. The results not only provide comprehensive genetic information for understanding the molecular mechanisms of isoquinoline alkaloid biosynthesis but also lay a foundation for the combinatory usage of the medicinal active ingredient of P. amurense.

The effect of slow breathing exercise on heart rate and blood pressure in patients undergoing percutaneous coronary intervention: a randomized controlled trial.

AIM: To determine the effects of slow breathing exercise (SBE) on heart rate (HR) and blood pressure (BP) in patients after percutaneous coronary intervention (PCI). METHODS AND RESULTS: The study is a single-blind, randomized controlled trial. Seventy-eight eligible patients after primary PCI were divided randomly into either the control group or the trial group. The control group only received routine post-PCI care. In addition to routine care, participants in the trial group performed SBE at home, two to three times for a total of 30 min every day for 12 weeks. The main outcomes were HR and BP measured in the office and at home. The secondary outcome was compliance with the breathing exercise. Patients allocated to the trial group, on average, performed 5.21 days/week for 26.00 min/day. The trial group showed a significant reduction in HR of 3.95 b.p.m. (P = 0.004) measured in the office. The reduction in HR measured in the office was greater for the trial group, with a significant difference between the two groups (P = 0.005). There was no significant difference between the two groups in HR measured at home. There was also no significant difference in BP measured in the office or at home between the two groups. CONCLUSION: Slow breathing exercise is an effective non-pharmacological method to reduce HR in patients undergoing PCI. Further study is needed to confirm whether the intervention is effective on BP. REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry: ChiCTR-IOR-17012525.

A Qualitative Exploration of the Psychological Experience of Patients Hospitalized With COVID-19.

This qualitative study describes the psychological experience of patients hospitalized with COVID-19. These patients went through 3 psychological stages: extremely uncertainties during the initial diagnostic stage, complicated feelings of negativity during the treatment stage, and positive growth in the recovery stage. It is important for nurses to provide holistic care.

Molecularly annotation of mouse avatar models derived from patients with colorectal cancer liver metastasis.

Background: Liver is the most common metastatic site in advanced colorectal cancer. Most patients with colorectal cancer liver metastasis (CRLM) do not benefit from current treatment. Patient-derived xenografts (PDXs) with defined molecular signatures are attractive models for preclinical studies. Methods: Successfully established PDXs were evaluated to elucidate their fidelity of patients' biologic characteristics (pathologic, genetic and protein properties, together with chemosensitivity). The genomic variations of PDXs were analyzed by next-generation sequencing to explore the underlying molecular mechanism of metastasis and potential therapeutic targets. Results: CRLM (N=73) showed a significantly higher successful PDX establishment rate than primary specimens (N=26; 76.7% vs. 57.7%). CRLM PDXs recapitulated the pathologic, genetic and protein properties of parental tumors, as well as chemosensitivity. Frequent altered genes in PDXs showed high consistency compared to patients' genomic alterations and were enriched in MAPK, ErbB, cell cycle, focal adhesion pathways for CRLM PDXs, whereas primary tumor-derived PDXs only exhibited genomic variations involving ErbB and cell cycle. The genetic alterations showed high concordance between paired PDXs from primary and metastatic tissues, except for recurrent gene mutations (ARID1A, CDK8, ETV1, STAT5B and WNK3) and common copy number gains in chromosomes 20q (e.g., SRC/AURKA). Several potential drug targets such as KRAS, HER2, and FGFR2 were validated using corresponding inhibitors. Additionally, PDX models could also be used in screening efficient regimens for patients with no druggable alterations. Conclusion: This study has successfully established and validated a large panel of molecularly annotated platforms from patients with CRLM for preclinical studies.

Design and implementation of an Omaha System-based integrated nursing management model for patients with newly-diagnosed diabetes.

AIMS: The aim of the present paper was to establish and implement an integrated nursing management model for patients with newly-diagnosed type 2 diabetes mellitus (T2DM) based on the Omaha System and to explore its impact on blood glucose levels, quality of life, and diabetes knowledge in these patients. METHODS: A non-randomized concurrent controlled trial was designed and the study was conducted in a hospital on the east coast of China between September 2013 and November 2015. We screened for patients with newly-diagnosed T2DM in 12 clinics of 3 comprehensive hospitals. A total of 367 patients with newly-diagnosed T2DM were assigned into two groups. In the intervention group, patients received routine outpatient care plus integrated nursing management; in the control group, only routine outpatient care was given. Changes in blood glucose levels, quality of life, and diabetes knowledge in both groups before the intervention and 6 months after the intervention were observed and compared. RESULTS: At the 6months, blood glucose levels, quality of life, and diabetes knowledge in the intervention group were significantly superior to those in the control group (all P<0.01). CONCLUSIONS: The integrated nursing management model was able to improve patients' glucose levels, quality of life, and diabetes knowledge.

Coptisine, a natural alkaloid from Coptidis Rhizoma, inhibits plasmodium falciparum dihydroorotate dehydrogenase.

Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a promising drug target for antimalarial chemotherapy. In our continuous efforts to develop more potent PfDHODH inhibitors, a unique library of active ingredients from traditional Chinese medicine (TCM) has been collected and was screened in this study. Through the initial screening, we found that coptisine, a natural alkaloid from TCM Coptidis Rhizoma, was a novel and potent inhibitor of PfDHODH with an IC50 value of 1.83 ± 0.08 µm. At the same time, enzyme kinetic analysis using Lineweaver-Burk plot indicated that coptisine is an uncompetitive inhibitor for PfDHODH. Thermal shift assay and molecular docking simulation research reveal that coptisine is capable of binding with PfDHODH. Moreover, coptisine exhibits weak inhibition activity against human DHODH, indicating that coptisine is a selective inhibitor of PfDHODH. Taken together, our study highlights the potential of active ingredients in TCM as valuable resource for discovering novel chemical scaffolds for PfDHODH.

Leaf N and P stoichiometry in relation to leaf shape and plant size for Quercus acutissima provenances across China.

Plant stoichiometry in relation to the structure and function of biological systems has been investigated at multiple scales. However, few studies have focused on the roles of stoichiometry for a given species. In this study, we determined leaf N and P stoichiometry, leaf shape and plant size in three Quercus acutissima common gardens with different climatic and site conditions. In the three common gardens, leaf N and P stoichiometry was significantly correlated with leaf shape and plant size, suggesting that leaf N and P stoichiometry affects the morphological performance of the leaves and stem. The scaling slopes of the relationships between leaf N and P stoichiometry and leaf shape ranged from |0.12| to |1.00|, while the slopes of the relationships between leaf N and P stoichiometry and plant size ranged from |0.95| to |2.66|. These results suggest that non-functional tissues (stem) are more susceptible to leaf nutrition than functional tissues (leaves), and leaf stoichiometry is more important in the construction of non-functional tissues (stem). Between the northernmost and southernmost common gardens, leaf N and leaf width (W), N:P and stem height (H), and N:P and stem diameter (D) showed significant covariations, which indicates that leaf N and W, N:P and plant size exhibit similar plastic responses to environmental change.

Optimization of micronutrient supplement for enhancing biogas production from food waste in two-phase thermophilic anaerobic digestion.

The aim of this study was to enhance the biogas productivity of two-phase thermophilic anaerobic digestion (AD) using food waste (FW) as the primary substrate. The influence of adding four trace metals (Ca, Mg, Co, and Ni) as micronutrient supplement in the methanogenic phase of the thermophilic system was investigated. Initially, Response Surface Methodology (RSM) was applied to determine the optimal concentration of micronutrients in batch experiments. The results showed that optimal concentrations of 303, 777, 7 and 3mg/L of Ca, Mg, Co and Ni, respectively, increased the biogas productivity as much as 50% and significantly reduced the processing time. The formulated supplement was tested in continuous two-phase thermophilic AD system with regard to process stability and productivity. It was found that a destabilized thermophilic AD process encountering high VFA accumulation recovered in less than two weeks, while the biogas production was improved by 40% yielding 0.46L CH4/gVSadded/day. There was also a major increase in soluble COD utilization upon the addition of micronutrient supplement. The results of this study indicate that a micronutrient supplement containing Ca, Mg, Co and Ni could probably remedy any type of thermophilic AD process.

Co-composting of horticultural waste with fruit peels, food waste, and soybean residues.

Horticultural waste was co-composted with fruit peels, food waste, and soybean residues individually to evaluate the effects of these easily available organic wastes in Singapore on the composting process and product quality. Each co-composting material was mixed with horticultural waste in the wet weight ratio of 1:1 and composted for 46 days. Results showed that all co-composting materials accelerated the degradation of total carbon and resulted in higher nutrients of nitrogen (N), phosphorous (P), and potassium (K) in the final product compared with horticultural waste alone. Mixture with fruit peels achieved the fastest total carbon loss; however, did not reach the minimum required temperature for pathogen destruction. The end product was found to be the best source for K and had a higher pH that could be used for the remediation of acidic soil. Food waste resulted in the highest available nitrate (NO3-N) content in the end product, but caused high salt content, total coliforms, and slower total carbon loss initially. Soybean residues were found to be the best co-composting material to produce compost with high N, P, and K when compared with other materials due to the highest temperature, fastest total carbon loss, fastest reduction in C/N ratio, and best conservation of nutrients.

Urban nutrient recovery from fresh human urine through cultivation of Chlorella sorokiniana.

High rate food consumption in urban cities causes vast amounts of nitrogen and phosphorus used in agriculture to end up in urban wastewaters. To substantially recover these nutrients, source-separated human urine should be targeted. The present study was to investigate the feasibility of recovering nitrogen and phosphorus in urine via microalgae cultivation. In concentrated urine, urea hydrolysis and precipitation occur rapidly, making microalgal growth difficult and nutrient recovery ineffective. However, when fresh urine was added as nutrient stock for 1-day growth requirement, biomass of Chlorella sorokiniana grew from 0.44 to 0.96 g L(-1) utilising 62.64 mg L(-1) of N and 10.64 mg L(-1) of P, achieving 80.4% and 96.6% recoveries, respectively in a 1-day non-sterile cultivation cycle. Overall, microalgae grown with urine added as nutrient supplement show no signs of inferiority as compared to those grown in recipe medium BG11 in terms of mass and chlorophyll a growth rates as well as resulting lipids (36.8%) and energy contents (21.0 kJ g(-1)).

Characterization of induced struvite formation from source-separated urine using seawater and brine as magnesium sources.

Struvite (MgNH4PO4·6H2O) precipitation is widely used for nutrient recovery from source-separated urine in view of limited natural resources. Spontaneous struvite formation depletes the magnesium in hydrolyzed urine so that additional magnesium source is required to produce induced struvite for P-recovery. The present study investigated the morphology and purity of induced struvite crystals obtained from hydrolyzed urine by using seawater and desalination brine as low cost magnesium sources. The results demonstrated that both seawater and brine were effective magnesium sources to recover phosphorus from hydrolyzed urine. Crystals obtained from synthetic and real urine were revealed that the morphology was feather and coffin shape, respectively. Structural characterization of the precipitates confirmed that crystallized struvite was the main product. However, co-precipitates magnesium calcite and calcite were observed when seawater was added into synthetic and real urine, respectively. It was found that the presence of calcium in the magnesium sources could compromise struvite purity. Higher struvite purity could be obtained with higher Mg/Ca ratio in the magnesium source. Comparative analysis indicated that seawater and brine had similar effect on the crystallized struvite purity.

A strategy for urban outdoor production of high-concentration algal biomass for green biorefining.

The present study was to investigate the feasibility of carrying out effective microalgae cultivation and high-rate tertiary wastewater treatment simultaneously in a vertical sequencing batch photobioreactor with small areal footprint, suitable for sustainable urban microalgae production. For 15 consecutive days, Chlorella sorokiniana was cultivated in synthetic wastewater under various trophic conditions. A cycle of 12-h heterotrophic: 12-h mixotrophic condition produced 0.98 g l(-1) d(-1) of algal biomass in tandem with a 94.7% removal of 254.4 mg l(-1) C-acetate, a 100% removal of 84.7 mg l(-1) N-NH4 and a removal of 15.0 mg l(-1) P-PO4. The cells were harvested via cost-effective chitosan flocculation with multiple dosing (3 times) applying established chitosan:cell ratio (1:300 w/w) and pH control (6.3-6.8). Reproducible flocculation efficiencies of greater than 99% and high-concentration algal broths (>20% solids) were achieved.

Combination teriparatide and raloxifene therapy for postmenopausal osteoporosis: results from a 6-month double-blind placebo-controlled trial.

UNLABELLED: We compared combination treatment with teriparatide plus raloxifene with teriparatide alone in women with postmenopausal osteoporosis in a 6-month double-blind, placebo-controlled trial that measured biochemical markers of bone turnover and BMD. Markers of bone formation and spine BMD increased similarly with teriparatide alone and combination therapy. However, combination therapy induced a significantly smaller increase in bone resorption versus teriparatide alone and significantly increased total hip BMD versus baseline. INTRODUCTION: The effects of combining two approved treatments for osteoporosis with different modes of action were examined by comparing teriparatide [rhPTH(1-34)] monotherapy with combination teriparatide and raloxifene therapy. MATERIALS AND METHODS: A 6-month randomized, double-blind trial comparing teriparatide plus raloxifene (n = 69) versus teriparatide plus placebo (n = 68) was conducted in postmenopausal women with osteoporosis. RESULTS: Bone formation (N-terminal propeptide of type 1 collagen [PINP]) increased similarly in both treatment groups. However, the increase in bone resorption (serum C-terminal telopeptide of type I collagen [CTx]) in the combination group was significantly smaller than in the teriparatide-alone group (p = 0.015). Lumbar spine BMD significantly increased 5.19 +/- 0.67% from baseline in the teriparatide-alone group. In the combination group, lumbar spine (6.19 +/- 0.65%), femoral neck (2.23 +/- 0.64%), and total hip (2.31 +/- 0.56%) BMD significantly increased from baseline to study endpoint, and the increase in total hip BMD was significantly greater than in the teriparatide-alone group (p = 0.04). In the teriparatide-alone group, mean serum calcium levels increased from baseline to endpoint (0.30 +/- 0.06 mg/dl, p < 0.001), whereas mean serum phosphate remained unchanged. In the combination group, mean serum calcium was unchanged, and mean serum phosphate decreased (-0.20 +/- 0.06 mg/dl, p < 0.001) from baseline to endpoint. Changes in serum calcium (p < 0.001) and phosphate (p < 0.004) were significantly different between treatment groups. The safety profile of combination therapy was similar to teriparatide alone. CONCLUSIONS: Combination therapy increased bone formation to a similar degree as teriparatide alone. However, the increase in bone resorption was significantly less and total hip BMD significantly increased for combination therapy compared with teriparatide alone. Combination treatment with raloxifene may thus enhance the bone forming effects of teriparatide. Further studies over longer treatment duration that include fracture endpoints are necessary to fully ascertain the clinical significance of combination raloxifene plus teriparatide therapy in postmenopausal osteoporosis.

Biotransformation of vegetable and fruit processing wastes into yeast biomass enriched with selenium.

Water extracts of cabbage, watermelon, a mixture of residual biomass of green salads and tropical fruits were used for yeast cultivation. These extracts contained from 1420 to 8900 mg/l of dissolved organic matter, and from 600 to 1800 mg/l of nitrogen. pH of the extracts was in the range from 4.1 to 6.4. Biomass concentration of yeast, Saccharomyces cerevisiae CEE 12 grown at 30 degrees C for 96 h in the sterilized extracts without any nutrient supplements was from 6.4 to 8.2 g/l; content of protein was from 40% to 45% of dry biomass. The yield was comparable with the yield of yeast biomass grown in potato dextrose broth. The biomass can be considered as the protein source. Its feed value was enhanced by incorporation of selenium in biomass to the level of 150 microg/g of dry biomass. Therefore, it was recommended to transform the extracts from vegetable and fruit processing wastes into the yeast biomass enriched with selenium.