Prediction of potential mechanisms of rhubarb therapy for colorectal cancer based on network pharmacological analysis and molecular docking.

The objective of this study was to investigate the potential targets and mechanism of Rheum palmatum L in the treatment of colorectal cancer based on the network pharmacology and molecular docking, which could provide the theoretical basis for clinical applications. The potential components were screened using TCMSP database and articles. The gene targets of colorectal cancer were screened through the Genecards database and Online Mendelian Inheritance in Man database. Then, the common targets of components and colorectal cancer were used to construct the network diagram of active components and targets in Cytoscape 3.7.0. The protein-protein interaction (PPI) diagram was generated using String database, and the targets were further analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes. Molecular docking between gene targets and active components was analyzed via AutoDock, and visualized through PyMol. Among this study, main targets might be TP53, EGF, MYC, CASP3, JUN, PTGS2, HSP90AA1, MMP9, ESR1, PPARG. And 10 key elements might associate with them, such as aloe-emodin, beta-sitosterol, gallic acid, eupatin, emodin, physcion, cis-resveratrol, rhein, crysophanol, catechin. The treatment process was found to involve nitrogen metabolism, p53 signaling pathway, and various cancer related pathway, as well as the AGE-RAGE signaling pathway, estrogen signaling pathway, interleukin-17 signaling pathway and thyroid hormone signaling pathway. The molecular docking was verified the combination between key components and their respective target proteins. Network pharmacological analysis demonstrated that R palmatum was could regulated p53, AGE-RAGE, interleukin-17 and related signaling pathway in colorectal cancer, which might provide a scientific basis of mechanism.

Transcriptomic Analysis of the Reduction in Seed Oil Content through Increased Nitrogen Application Rate in Rapeseed (Brassica napus L.).

Nitrogen is essential for improving the seed oil yield of rapeseed (Brassica napus L.). However, the molecular mechanism by which increased nitrogen rates impact seed oil content is largely unknown. Therefore, a field experiment was conducted to determine how three nitrogen application rates (120, 240, and 360 kg ha-1) regulated seed oil content via transcriptomic analysis. The results showed that the seed yield and the protein and total N contents increased from N1 to N3, with average increases of 57.2%, 16.9%, and 79.5%, respectively. However, the seed oil content significantly decreased from N1 to N3, with an average decrease of 8.6%. These results were repeated over a number of years. The quantity of oil protein bodies observed under a transmission electron microscope was in accordance with the ultimate seed oil and protein contents. As the nitrogen application rate increased, a substantial number of genes involved in the photosynthesis, glycolysis, and phenylpropanoid biosynthesis pathways were up-regulated, as were TF families, such as AP2/ERF, MYB, and NAC. The newly identified genes were mainly involved in carbohydrate, lipid, and amino acid metabolism. Metabolic flux analysis showed that most of the genes involved in glycolysis and fatty acid biosynthesis had higher transcript levels in the early development stages. Our results provide new insights into the molecular regulation of rapeseed seed oil content through increased nitrogen application rates.

Haplotype-resolved genome of diploid ginger (Zingiber officinale) and its unique gingerol biosynthetic pathway.

Ginger (Zingiber officinale), the type species of Zingiberaceae, is one of the most widespread medicinal plants and spices. Here, we report a high-quality, chromosome-scale reference genome of ginger 'Zhugen', a traditionally cultivated ginger in Southwest China used as a fresh vegetable, assembled from PacBio long reads, Illumina short reads, and high-throughput chromosome conformation capture (Hi-C) reads. The ginger genome was phased into two haplotypes, haplotype 1 (1.53 Gb with a contig N50 of 4.68 M) and haplotype 0 (1.51 Gb with a contig N50 of 5.28 M). Homologous ginger chromosomes maintained excellent gene pair collinearity. In 17,226 pairs of allelic genes, 11.9% exhibited differential expression between alleles. Based on the results of ginger genome sequencing, transcriptome analysis, and metabolomic analysis, we proposed a backbone biosynthetic pathway of gingerol analogs, which consists of 12 enzymatic gene families, PAL, C4H, 4CL, CST, C3'H, C3OMT, CCOMT, CSE, PKS, AOR, DHN, and DHT. These analyses also identified the likely transcription factor networks that regulate the synthesis of gingerol analogs. Overall, this study serves as an excellent resource for further research on ginger biology and breeding, lays a foundation for a better understanding of ginger evolution, and presents an intact biosynthetic pathway for species-specific gingerol biosynthesis.

Chinese herbal compound combined with western medicine therapy in the treatment of plasma cell mastitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Plasma cell mastitis (PCM) is a benign suppurative disease of the breast based on the expansion of mammary ducts and infiltration of plasma cells. It is relatively rare clinically, and its main manifestations include nonperiodic breast pain, nipple discharge, areola lump, nipple depression, nipple fistula, among others. Modern medicine is mainly surgical treatment, which is easy to recur. The clinical practice shows that the overall treatment of patients with TCM syndrome differentiation using oral medicine combined with western medicine therapy, combined internal and external treatment, can significantly improve the curative effect, prevent recurrence, has a certain therapeutic advantage, but lack of evidence of evidence-based medicine. The purpose of this study is to study the efficacy and safety of oral traditional Chinese medicine (TCM) combined with western medicine therapy in the treatment of PCM. METHODS: Use computer to retrieve English databases (PubMed, Embase, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wan Fang, VIP, Chinese biomedical database), from the establishment of database to September 2020, for randomized controlled trials(RCTs) of oral TCM combined with western medicine therapy in the treatment of PCM, two researchers independently extracted the data and evaluated the quality of the included research, and meta-analysis was conducted on the included literatures using RevMan5.3 software. RESULTS: This study evaluated the efficacy and safety of oral TCM combined with western medicine therapy in the treatment of PCM from the aspects of effective rate, symptom score, recurrence rate, adverse reaction rate, and patient satisfaction. CONCLUSION: This study will provide reliable evidence-based evidence for the clinical application of oral TCM combined with western medicine therapy in the treatment of PCM. ETHICS AND DISSEMINATION: The purpose of this study is to sort out and analyze the literature. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences. OSF REGISTRATION NUMBER:: doi 10.17605/OSF.IO/K9A78.

Anti-diabetic effects of the fraction of alkaloids from Ramulus Mori, an innovative Sangzhi alkaloids as an α-glucosidase inhibitor / 药学学报

Sangzhi alkaloids (SZ-A) are derived from traditional Chinese medicine Ramulus Mori, serving well as an innovative antidiabetic drug, due to α-glucosidase inhibition. To evaluate the potency of glucosidase inhibitory effect of SZ-A, the enzyme-based screening platforms, including sucrase, maltase and amylase were established, and IC50 was calculated. The effects of SZ-A on postprandial blood glucose at a single dose, oral sucrose, starch and glucose loading were determined in normal ICR mice and alloxan-induced hyperglycemic mice. To confirm the anti-diabetic effects of SZ-A on glucose and lipid metabolism after long-term administration, the postprandial and fasting blood glucose, serum insulin, urinary glucose levels, glycosylated serum proteins and blood lipid levels were determined in high-fat fed C57 obese mice (pre-diabetic HFC57 mice) and diabetic rats induced by streptozotocin (STZ). The Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College approved all of the protocols for this research. We found that SZ-A exhibited a significant inhibitory effect on the sucrase and maltase. SZ-A showed no effect on amylase. In normal ICR mice and alloxan-induced hyperglycemic mice, SZ-A at a single dose significantly delayed and reduced the peak of blood glucose after sucrose or starch loading, but showed no effect on the increase of blood glucose after glucose loading. In STZ diabetic rats, SZ-A significantly reduced the postprandial or fasting blood glucose levels, glycosylated serum proteins and urinary glucose. SZ-A also reduced serum triglyceride (TG) and cholesterol (TC) levels after 3 weeks of treatment. SZ-A ameliorated the postprandial blood glucose or the fasting blood glucose elevation, and reduced the incidence of hyperglycemia in HFC57 mice. SZ-A decreased the basal insulin level, improved insulin sensitivity, and ameliorated glucose intolerance in pre-diabetic HFC57 mice. Our results indicated that SZ-A had a novel inhibitory activity on α-glucosidase, especially on disaccharidases. SZ-A at a single dose significantly reduced the peak of blood glucose elevation and delayed the increase of blood glucose in normal and diabetic mice after disaccharide and polysaccharide loading. Long-term SZ-A treatment improved glucose and lipid metabolic profiles by delaying carbohydrate absorption from the intestine and reduced the postprandial blood glucose levels in both pre-diabetic and diabetic animal models. Therefore, SZ-A application may display a beneficial role in preventing the development and complications of diabetes.

Sodium tanshinone IIA sulfonate attenuates hemorrhagic shock-induced organ damages by nuclear factor-kappa B pathway.

BACKGROUND: Trauma resulted hemorrhagic shock (HS) leads to increased oxidative stress and inflammatory responses, which contributes greatly to organ failure or dysfunction. Tanshinone IIA sulfonate (TSA), as an antioxidant, may potentially be used in fluid resuscitation to prevent HS-induced organ damages. METHODS: In this study, a rat HS model was constructed. HS rats received TSA or vehicle drug during resuscitation. Mean arterial pressure and factors associated with organ failure or dysfunction, oxidative stress, and inflammatory response were investigated to evaluate treatment responses. Expression of proteins in NF-кB pathway was evaluated to elucidate the mechanism of TSA in preventing HS-induced organ damage. RESULTS: Although HS induced organ damage and upregulated oxidative stress and inflammatory response, TSA treatment ameliorated organ dysfunction, reduced oxidative stress, and suppressed inflammatory responses. We also showed that TSA treatment attenuated HS-induced activation in NF-кB pathway. CONCLUSIONS: TSA can potentially serve as an antioxidant for ameliorating HS-induced organ failure or function. Its mechanism of action may be through inhibiting NF-кB pathway.

Formulation, characterization and hypersensitivity evaluation of an intravenous emulsion loaded with a paclitaxel-cholesterol complex.

The objective of this paper was to develop a novel Cremophor-free, autoclave stable, intravenous emulsion for paclitaxel (PACE). A paclitaxel-cholesterol complex was used as the drug carrier to improve the solubility of paclitaxel in the oil phase of emulsions. The complex and PACE were prepared by rotary evaporation and high-pressure homogenization, respectively. Effects of oil phases, emulsifiers and pH values on the characteristics of PACE were investigated. PACE was characterized with regard to its appearance, morphology, osmolality, pH value, particle size, zeta potential, encapsulation efficiency and stability. Hypersensitivity was evaluated by guinea pig hypersensitivity reaction. The final formulation was composed of the complex, soybean oil, medium-chain triglyceridel, soybean lecithin, poloxamer 188 and glycerol. The resulting PACE had an encapsulation efficiency of 97.3% with a particle size of 135 nm and a zeta potential of -38.3 mV. Osmolality and pH of the formulation were 383 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115 °C for 30 min and remained stable for at least 12 months at 6 °C. PACE also exhibited a better tolerance than an equal dose of Cremophor-based paclitaxel injection in guinea pigs, as no obvious hypersensitivity reaction was observed. These results suggested that PACE has a great potential for industrial-scale production and clinical applications.

Effects of warm-supplementing kidney yang (WSKY) capsule added on risperidone on cognition in chronic schizophrenic patients: a randomized, double-blind, placebo-controlled, multi-center clinical trial.

OBJECTIVE: To evaluate the effects of warm-supplementing kidney yang (WSKY) capsule added on risperidone on cognition in chronic schizophrenic patients. METHODS: A randomized, double-blind, placebo-controlled, multi-center clinical trial was conducted. All 200 patients who met the DSM-IV diagnostic criteria for schizophrenia were randomly assigned to double-blind treatment with WSKY capsule (n = 100) or placebo (n = 100) added on risperidone for 8 weeks. The primary outcome measure was the cognitive function assessment assessed by the classic form of the Wisconsin Card Sorting Test (WCST) at baseline and week 8. The secondary outcome measures were assessed including the positive and negative symptoms scale (PANSS), the social disability screening schedule (SDSS), and the Hamilton rating scale for depression (HAM-D-17) at baseline, week 2, week 4, and week 8. The extrapyramidal side effects were assessed each week using the abnormal involuntary movement scale (AIMS) and rating scale for extrapyramidal side effects (RSESE), while adverse events were assessed using treatment emergent symptoms scale (TESS) as additional indicators of tolerability throughout the trial. RESULTS: The response rates of the WSKY group for the number of completed categories (CC), errors responses number (ER), perseveringly errors responses number (PER), and conceptual level (CL) of WCST assessment were significantly higher than those of placebo. The reduction in the SDSS score from baseline to endpoint was significantly greater in the WSKY group than those in the placebo. There were no significant differences in the response rates for the correct responses number, perseveringly responses number (PR) of WCST between the treatment groups. The improvements in the WCST indexes, PANSS score, HAM-D-17 score were no significant differences from baseline to endpoint between the two groups at week 8. There were no significant differences in AIMS, RSESE, and TESS compared patients treated with WSKY capsule with those in placebo during treatment. CONCLUSION: WSKY capsule added on risperidone may improve cognitive function, social function of the chronic schizophrenic patients, and the WSKY safely during treatment.

Effectiveness and tolerability of warm-supplementing kidney yang added to risperidone in improving cognitive impairment in patients with schizophrenia: An 8-week, multicenter, randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Certain herbal medicines have been reported to be effective in the treatment of psychiatric conditions, and combination treatment with drugs and herbal medicines has been reported to be useful in enhancing treatment efficacy and reducing recovery time and adverse events (AEs). OBJECTIVE: The purpose of this study was to investigate the effectiveness and tolerability of warm-supplementing kidney yang (WSKY) added to risperidone in improving cognitive impairment and negative symptoms (ie, cognitive function) in patients with schizophrenia. METHODS: This 8-week, multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in patients who met the clinical classification for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were recruited from 3 centers (including inpatient and outpatient clinics) and were evenly randomized to receive WSKY or placebo added to risperidone for 8 weeks. Primary assessments were conducted at weeks 2, 4, and 8. A clinical response was defined as a ≥50% reduction score (from baseline) on the Positive and Negative Syndrome Scale (PANSS), a ≥30% reduction score (from baseline) on the Scale for the Assessment of Negative Symptoms (SANS), or a ≥50% reduction score (from baseline) on the Hamilton Rating Scale for Depression (HAM-D-17). Cognitive function was assessed using the Wisconsin Card Sorting Test (WCST) at baseline and end point. Extrapyramidal AEs were assessed weekly using the Abnormal Involuntary Movement Scale (AIMS) and the Rating Scale for Extrapyramidal Side Effects (RSESE). AEs were assessed by patient interviews conducted at each clinic visit and also by the Treatment Emergent Symptoms Scale (TESS) scores. RESULTS: One-hundred twenty patients (62 males, 58 females; mean [SD] age, 34.4 [9.4] years; range, 18-45 years; baseline mean [SD] PANSS score, 88.7 [12.3]) were included in this study. Risperidone- and WSKY-treated patients had statistically significant improvements at end point in the number of completed categories (P = 0.019), perseverative responses (P = 0.041), perseverative errors (P = 0.040), and total errors (P = 0.049) on the WCST compared with placebo. The improvements in the PANSS, SANS, and HAM-D-17 scores were not significantly different between the 2 groups at week 8 for observed case and last-observation-carried-forward (LOCF) analyses. The response rates (LOCF) for the PANSS scores in the WSKY and placebo groups were 55.0% and 35.0%, respectively (P = 0.028), while the SANS scores were 63.3% and 45.0% (P = 0.044) and the HAM-D-17 were 35.0% and 45.0% (P = 0.264). There were no significant between-group differences in scores on the AIMS, RSESE, or TESS. CONCLUSIONS: The results of this study suggest that WSKY added to risperidone significantly improved cognitive function in these patients, as measured by the number of completed categories, perseverative responses, perseverative errors, and total errors on the WCST compared with placebo. The response rates in the WSKY group for the PANSS and SANS scores were significantly higher compared with placebo. All treatments were generally well tolerated.

[Effects of Shenggu injection on mRNA expression of vascular endothelia growth factor in rat osteoblasts in vitro].

OBJECTIVE: To study the effects of Shenggu injection (SGI) on mRNA expression of vascular endothelia growth factor (VEGF) in rat osteoblasts in vitro and to explore its possible molecular mechanisms in promoting fracture healing. METHODS: Rat osteoblasts cultured in vitro were stimulated with SGI according to the protocol. The expression levels of VEGF mRNA in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction (RT-PCR). RESULTS: When osteoblasts were stimulated with different concentrations of SGI for 5 days, the expression of VEGF mRNA peaked with 1 mg/ml SGI on the 5th day. When treated with 1 mg/ml SGI from the 1st to the 5th day, the expression of VEGF mRNA increased gradually with the increase of culturing time. CONCLUSION: SGI could promote significantly the expression of VEGF mRNA in rat osteoblasts in vitro. The levels of expression of VEGF mRNA changed along with different concentrations and stimulating time of SGI.

Effects of Shenggu injection on mRNA expression of vascular endothelia growth factor in rat osteoblasts in vitro / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the effects of Shenggu injection (SGI) on mRNA expression of vascular endothelia growth factor (VEGF) in rat osteoblasts in vitro and to explore its possible molecular mechanisms in promoting fracture healing.</p><p><b>METHODS</b>Rat osteoblasts cultured in vitro were stimulated with SGI according to the protocol. The expression levels of VEGF mRNA in the cells in every group were examined by reverse-transcriptase ploymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>When osteoblasts were stimulated with different concentrations of SGI for 5 days, the expression of VEGF mRNA peaked with 1 mg/ml SGI on the 5th day. When treated with 1 mg/ml SGI from the 1st to the 5th day, the expression of VEGF mRNA increased gradually with the increase of culturing time.</p><p><b>CONCLUSION</b>SGI could promote significantly the expression of VEGF mRNA in rat osteoblasts in vitro. The levels of expression of VEGF mRNA changed along with different concentrations and stimulating time of SGI.</p>