Enzymatic activity of 38 CYP2C9 genotypes on ibuprofen.

BACKGROUND AND OBJECTIVE: Ibuprofen, a common non-steroidal anti-inflammatory drug, is used clinically for pain relief and antipyretic treatment worldwide. However, regular or long-term use of ibuprofen may lead to a series of adverse reactions, including gastrointestinal bleeding, hypertension and kidney injury. Previous studies have shown that CYP2C9 gene polymorphism plays an important role in the elimination of various drugs, which leads to the variation in drug efficacy. This study aimed to evaluate the effect of 38 CYP2C9 genotypes on ibuprofen metabolism. METHODS: Thirty-eight recombinant human CYP2C9 microsomal enzymes were obtained using a frugiperda 21 insect expression system according to a previously described method. Assessment of the catalytic function of these variants was completed via a mature incubation system: 5 pmol CYP2C9*1 and 38 CYP2C9 variants recombinant human microsomes, 5 µL cytochrome B5, ibuprofen (5-1000 µM), and Tris-HCl buffer (pH 7.4). The ibuprofen metabolite contents were determined using HPLC analysis. HPLC analysis included a UV detector, Plus-C18 column, and mobile phase [50% acetonitrile and 50% water (containing 0.05% trifluoroacetic acid)]. The kinetic parameters of the CYP2C9 genotypes were obtained by Michaelis-Menten curve fitting. RESULTS: The intrinsic clearance (CLint) of eight variants was not significantly different from CYP2C9*1; four CYP2C9 variants (CYP2C9*38, *44, *53 and *59) showed significantly higher CLint (increase by 35%-230%) than that of the wild-type; the remaining twenty-six variants exhibited significantly reduced CLint (reduced by 30%-99%) compared to that of the wild-type. CONCLUSION: This is the first systematic evaluation of the catalytic characteristics of 38 CYP2C9 genotypes involved ibuprofen metabolism. Our results provide a corresponding supplement to studies on CYP2C9 gene polymorphisms and kinetic characteristics of different variants. We need to focus on poor metabolizers (PMs) with severely abnormal metabolic functions, because they are more susceptible to drug exposure.

UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals Potential Anti-tumor Mechanism of Banxia Xiexin Decoction in Colorectal Cancer Mice.

OBJECTIVE: To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. METHODS: Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. RESULTS: Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. CONCLUSION: BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.

Physiological and Transcriptome Analyses Revealed the Mechanism by Which Deferoxamine Promotes Iron Absorption in Cinnamomum camphora.

Iron deficiency causes chlorosis and growth inhibition in Cinnamomum camphora, an important landscaping tree species. Siderophores produced by plant growth-promoting rhizobacteria have been widely reported to play an indispensable role in plant iron nutrition. However, little to date has been determined about how microbial siderophores promote plant iron absorption. In this study, multidisciplinary approaches, including physiological, biochemical and transcriptome methods, were used to investigate the role of deferoxamine (DFO) in regulating Fe availability in C. camphora seedlings. Our results showed that DFO supplementation significantly increased the Fe2+ content, SPAD value and ferric-chelate reductase (FCR) activity in plants, suggesting its beneficial effect under Fe deficiency. This DFO-driven amelioration of Fe deficiency was further supported by the improvement of photosynthesis. Intriguingly, DFO treatment activated the metabolic pathway of glutathione (GSH) synthesis, and exogenous spraying reduced glutathione and also alleviated chlorosis in C. camphora. In addition, the expression of some Fe acquisition and transport-related genes, including CcbHLH, CcFRO6, CcIRT2, CcNramp5, CcOPT3 and CcVIT4, was significantly upregulated by DFO treatment. Collectively, our data demonstrated an effective, economical and feasible organic iron-complexing agent for iron-deficient camphor trees and provided new insights into the mechanism by which siderophores promote iron absorption in plants.

Analyses and identification of ICD codes for dementias in the research based on the NHIRD: a scoping review protocol.

INTRODUCTION: Studies based on health claims data (HCD) have been increasingly adopted in medical research for their strengths in large sample size and abundant information, and the Taiwan National Health Insurance Research Database (NHIRD) has been widely used in medical research across disciplines, including dementia. How the diagnostic codes are applied to define the diseases/conditions of interest is pivotal in HCD-related research, but the consensus on the issue that diagnostic codes most appropriately define dementias in the NHIRD is lacking. The objectives of this scoping review are (1) to investigate the relevant characteristics in the published reports targeting dementias based on the NHIRD, and (2) to address the diversity by a case study. METHODS AND ANALYSIS: This scoping review protocol follows the methodological framework of the Joanna Briggs Institute Reviewer's Manual and the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. The review will be performed between 1 March and 31 December 2022 in five stages, including identifying the relevant studies, developing search strategies, individually screening and selecting evidence, collecting and extracting data, and summarising and reporting the results. The electronic databases of MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, Airiti Library Academic Database, the National Health Insurance Administration's repository, and Taiwan Government Research Bulletin will be searched. We will perform narrative syntheses of the results to address research questions and will analyse the prevalence across the included individual studies as a case study. ETHICS AND DISSEMINATION: Our scoping review is a review of the published reports and ethical approval is not required. The results will provide a panorama of the dementia studies based on the NHIRD. We will disseminate our findings through peer-reviewed journals and conferences, and share with stakeholders by distributing the summaries in social media and emails.

Isolation and Characterization of an LBD Transcription Factor CsLBD39 from Tea Plant (Camellia sinensis) and Its Roles in Modulating Nitrate Content by Regulating Nitrate-Metabolism-Related Genes.

Nitrate nitrogen is an important nitrogen source for tea plants' growth and development. LBD transcription factors play important roles in response to the presence of nitrate in plants. The functional study of LBD transcription factors in tea plants remains limited. In this study, the LBD family gene CsLBD39 was isolated and characterized from tea plants. Sequence analysis indicated that CsLBD39 contained a highly conserved CX2CX6CX3CX domain. The phylogenetic tree assay showed that CsLBD39 belonged to class II subfamily of the LBD family. CsLBD39 was highly expressed in flowers and root; we determined that its expression could be induced by nitrate treatment. The CsLBD39 protein was located in the nucleus and has transcriptional activation activity in yeast. Compared with the wild type, overexpression of CsLBD39 gene in Arabidopsis resulted in smaller rosettes, shorter main roots, reduced lateral roots and lower plant weights. The nitrate content and the expression levels of genes related to nitrate transport and regulation were decreased in transgenic Arabidopsis hosting CsLBD39 gene. Compared with the wild type, CsLBD39 overexpression in transgenic Arabidopsis had smaller cell structure of leaves, shorter diameter of stem cross section, and slender and compact cell of stem longitudinal section. Under KNO3 treatment, the contents of nitrate, anthocyanins, and chlorophyll in leaves, and the content of nitrate in roots of Arabidopsis overexpressing CsLBD39 were reduced, the expression levels of nitrate transport and regulation related genes were decreased. The results revealed that CsLBD39 may be involved in nitrate signal transduction in tea plants as a negative regulator and laid the groundwork for future studies into the mechanism of nitrate response.

Exogenous Melatonin Enhances Photosynthetic Capacity and Related Gene Expression in A Dose-Dependent Manner in the Tea Plant (Camellia sinensis (L.) Kuntze).

The enhancement of photosynthesis of tea leaves can increase tea yield. In order to explore the regulation mechanism of exogenous melatonin (MT) on the photosynthetic characteristics of tea plants, tea variety 'Zhongcha 108' was used as the experimental material in this study. The effects of different concentrations (0, 0.2, 0.3, 0.4 mM) of melatonin on the chlorophyll (Chl) content, stomatal opening, photosynthetic and fluorescence parameters, antioxidant enzyme activity, and related gene expression of tea plants were detected and analyzed. The results showed that under 0.2-mM MT treatment, chlorophyll (Chl) content, photosynthetic rate (Pn), stomatal conductance (Gs), intercellular CO2 concentration (Ci), and transpiration rate (Tr) improved, accompanied by a decrease in stomata density and increase in stomata area. Zero point two millimolar MT increased Chl fluorescence level and superoxide dismutase (SOD) activity, and reduced hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents, indicating that MT alleviated PSII inhibition and improved photochemical efficiency. At the same time, 0.2 mM MT induced the expression of genes involved in photosynthesis and chlorophyll metabolism to varying degrees. The study demonstrated that MT can effectively enhance the photosynthetic capacity of tea plants in a dose-dependent manner. These results may promote a comprehensive understanding of the potential regulatory mechanism of exogenous MT on photosynthesis in tea plants.

The Impact of 52-Week Single Inhaler Device Triple Therapy versus Dual Therapy on the Mortality of COPD Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There are more single inhaler device triple therapy available for COPD patients now. However, the effect of long-term triple therapy fixed dose combination (FDC) on mortality remains unclear. This study aimed to evaluate the impact of one-year single inhaler device triple therapy, including long-acting ß2-agonists (LABAs), long-acting muscarinic receptor antagonists (LAMAs), and inhaled corticosteroids (ICSs), with dual therapies, comprised of either LABA/LAMA or ICS/LABA, on the mortality of patients with COPD. We searched the PubMed, Cochrane library, Web of Science, Embase databases, and clinical trial registry of clinicaltrials.gov and WHO ICTRP. Randomized controlled trials (RCTs) compared single inhaler device triple and dual therapies for 52 weeks were selected for the meta-analysis. The primary endpoint was all-cause mortality. A total of 6 RCTs were selected for the meta-analysis, including 10,274 patients who received single inhaler device triple therapy (ICS/LABA/LAMA FDC) and 12,395 patients who received ICS/LABA or LABA/LAMA dual therapy. Risk of death was significantly lower in the ICS/LABA/LAMA FDC group compared to the LABA/LAMA group (RR = 0.69, 95% CI = 0.53-0.90, p = 0.007). There was no significant difference in mortality between the ICS/LABA/LAMA FDC and ICS/LABA therapy groups (RR = 0.94, 95% CI = 0.72-1.24, p = 0.66). In addition, patients receiving ICS/LABA/LAMA FDC therapy had less moderate or severe exacerbations compared with the dual therapy groups (RR = 0.76, 95% CI = 0.73-0.80, p < 0.001 for LABA/LAMA; RR = 0.84, 95% CI = 0.78-0.90, p < 0.001 for ICS/LABA). By contrast, the risk of pneumonia in the ICS/LABA/LAMA FDC group was higher than in the LABA/LAMA group (RR = 1.43, 95% CI = 1.21-1.68, p < 0.001). In conclusion, ICS/LABA/LAMA FDC therapy could help improve the clinical outcomes of patients with COPD. However, triple therapy could increase the risk of pneumonia in comparison with LABA/LAMA dual therapy.

Liquid combination of hyaluronan, glucosamine, and chondroitin as a dietary supplement for knee osteoarthritis patients with moderate knee pain: A randomized controlled study.

BACKGROUND: Hyaluronan (HA), glucosamine, and chondroitin sulfate are widely consumed as dietary supplements for the treatment of knee osteoarthritis (OA). This study aimed to explore the efficacy and safety of a dietary liquid supplement mixture containing HA, glucosamine, and chondroitin in patients with knee OA who had moderate knee pain (visual analogue scale of 4-6 points). METHODS: This was a short-term, randomized, double-blind, placebo-controlled study. Subjects were allocated to administer either a bottle of 20 mL supplement mixture (50 mg HA plus 750 mg glucosamine plus 250 mg chondroitin, namely A + HA) or placebo once daily for 8 weeks. Outcome measures included the Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, 36-item Short Form Survey (SF-36), Chinese version of Pittsburgh Sleep Quality Index, and incidence of adverse event were evaluated at the end of week 8. Efficacy analyses were conducted in the modified intent-to-treat population. RESULTS: Of the 80 subjects in the modified intent-to-treat population, 39 received A + HA while 41 received placebo. After 8 weeks of treatment, the A + HA group failed to demonstrate a significant symptomatic efficacy and quality of life improvement in terms of Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36, and Chinese version of Pittsburgh Sleep Quality Index as compared to the placebo group. However, the mean changes in most of the SF-36 scale scores were numerically higher in the A + HA group than in the placebo group. No treatment-related adverse event was reported in both groups. CONCLUSIONS: This present study found that the combination of liquid low molecular weight HA, glucosamine, and chondroitin oral supplement did not effectively improve knee OA pain and symptoms after short-term use in knee OA patients with moderate knee pain. However, these results should be interpreted with caution due to the intrinsic limitation of the study design.

Single-cell RNA sequencing reveals that targeting HSP90 suppresses PDAC progression by restraining mitochondrial bioenergetics.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, which lacks effective treatment strategies. There is an urgent need for the development of new strategies for PDAC therapy. The genetic and phenotypic heterogeneity of PDAC cancer cell populations poses further challenges in the clinical management of PDAC. In this study, we performed single-cell RNA sequencing to characterize PDAC tumors from KPC mice. Functional studies and clinical analysis showed that PDAC cluster 2 cells with highly Hsp90 expression is much more aggressive than the other clusters. Genetic and pharmacologic inhibition of Hsp90 impaired tumor cell growth both in vitro and in vivo. Further mechanistic study revealed that HSP90 inhibition disrupted the interaction between HSP90 and OPA1, leading to a reduction in mitochondrial cristae amount and mitochondrial energy production. Collectively, our study reveals that HSP90 might be a potential therapeutic target for PDAC.

Exogenous melatonin positively regulates lignin biosynthesis in Camellia sinensis.

Melatonin (MT) is a bioactive molecule that can regulate various developmental processes. Changes in lignin content play important roles in plant growth and development. Herein, quantitative analysis and histochemical staining showed that lignin content significantly increased over time, and melatonin treatment triggered the lignification at 8 and 16 d in tea leaves. The POD activity participated in lignin formation had also been significantly improved. The effect of melatonin on the increase of lignin content was attenuation over time. Sequencing results based on transcriptome at 8 and 16 d showed that 5273 and 3019 differentially expressed genes (DEGs) were identified in CK1 vs. MT1 and CK2 vs. MT2, respectively. A total of 67 DEGs were annotated to lignin biosynthesis, and 38 and 9 genes were significantly up-regulated under melatonin treatment, respectively. Some transcription factor genes such as MYB were also identified among the two pairwise comparisons, which might relate to lignin metabolism. Melatonin increased the degree of lignification in tea leaves by modifying the enzyme genes expression involved in lignin synthesis pathway. These results provide a reference for further study on the molecular mechanism of the dynamic changes of lignin content induced by melatonin treatment in tea plants.

The effect of oral low molecular weight liquid hyaluronic acid combination with glucosamine and chondroitin on knee osteoarthritis patients with mild knee pain: An 8-week randomized double-blind placebo-controlled trial.

BACKGROUND: The popularity of dietary supplements for knee osteoarthritis (OA) management is on the rise; however, their effects are still debated. METHODS: This study aimed to investigate the effect of an oral low molecular weight liquid hyaluronic acid supplement in the treatment of knee OA patients with mild knee pain (visual analogue scale [VAS] ≤ 3) in Taiwan population. This was a randomized, double-blind, placebo-controlled study. Forty-seven subjects were enrolled and randomly allocated to either the A+HA or the placebo groups. The subjects were required to drink a bottle contained 20 mL of A+HA or placebo daily throughout an 8-week study period. The efficacy was assessed by using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 36-item Short Form Survey (SF-36). RESULTS: At Week 8, significant reductions from baseline in the WOMAC pain (-2.6 ±â€Š1.68, P < .0001), stiffness (-1.2 ±â€Š1.50, P = .007), physical function (-5.8 ±â€Š4.39, P < .0001), and total (-9.4 ±â€Š5.82, P < .0001) scores were observed in the A+HA group but not in the placebo group. Significant differences in the mean change of WOMAC scores from baseline at Week 8 between groups were detected (P < .01). At Week 8, the A+HA group also showed significant improvements in SF-36 physical functioning (2.7 ±â€Š3.10, P = .001) and bodily pain (0.7 ±â€Š1.50, P < .05) domains. Although the A+HA group had a higher increase in the SF-36 total score than the placebo group but the difference was not statistically significant (2.1 ±â€Š12.75 vs 0.3 ±â€Š19.66, P = .12). CONCLUSIONS: Oral administration of low molecular weight liquid HA appeared to be effective for knee OA patients with mild knee pain (VAS ≤ 3) in the relief of knee OA symptoms, particularly in pain and physical function.Clinical Trial Registration: NCT04352322.

Effectiveness comparisons of traditional Chinese medicine on treating diabetic nephropathy proteinuria: A systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is one of the microvascular complications of diabetes mellitus. Proteinuria is the most important clinical feature of DN and an independent risk factor for the progression of DN. Therefore, reducing urinary protein is the primary goal of DN treatment. Traditional Chinese medicine (TCM) has long been widely used in the treatment of DN. Therefore, this paper conducted a meta-analysis of the clinical efficacy of TCM in the treatment of DN proteinuria, to comprehensively analyze the role of TCM in the treatment of DN. METHODS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet, Nature, Science online and China Journal Full-text Database, China Biomedical Literature CD-ROM Database, and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to September 2019. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of DN proteinuria. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019139707.

The effects of single inhaler triple therapy vs single inhaler dual therapy or separate triple therapy for the management of chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.

Background: This study aims to compare the effects of single inhaler triple therapy comprised of inhaled corticosteroids (ICSs), long-acting ß2-agonists (LABAs), and long-acting muscarinic receptor antagonists (LAMAs) with dual therapies comprised of either LABA/LAMA, ICS/LABA or separate ICS/LABA plus LAMA triple therapy. Methods: The Pubmed, Embase, and Cochrane databases were searched up to October 31st 2018. Only randomized controlled trials were included in the meta-analysis. The primary outcome was the rate of moderate-to-severe chronic obstructive pulmonary disease (COPD) exacerbations. Results: Seven studies fulfilling the inclusion criteria were included in the meta-analysis. Single inhaler triple therapy was associated with a significantly lower risk of COPD exacerbation compared with LABA/LAMA (rate ratio, 0.69; 95% confidence interval [CI] 0.55 to 0.87, I2 =85%), and ICS/LABA (rate ratio, 0.81; 95% CI 0.73 to 0.89, I2 =29%) dual therapy. Single inhaler triple therapy led to a more significant improvement in lung function and quality of life compared with LABA/LAMA and ICS/LABA dual therapy. Single inhaler triple therapy was associated with a higher risk of pneumonia compared with LABA/LAMA (risk ratio, 1.38, 95% CI 1.14 to 1.67, I2 =0) dual therapy. Conclusions: The use of single inhaler triple therapy for COPD patients can result in lower rates of moderate or severe exacerbations of COPD as well as improved lung function and quality of life compared with dual therapy with LABA/LAMA or ICS/LABA.

[Meta-analysis of Yiqi Huoxue method in treating idiopathic membranous nephropathy].

The incidence of idiopathic membranous nephropathy (IMN) is increasing year by year, and the clinical research on Chinese medicine treatment of INM is also growing. This study aims to evaluate the efficiency and safety of Yiqi Huoxue method for IMN. Data sources used were from PubMed, EMbase, the Cochrane Library, CBM, CNKI, Wanfang and VIP database. Two researchers independently screened the literature and extracted data. RevMan 5.3 software was used for Meta analysis, and the evidences were graded for the outcomes according to GRADE system by using GRADEprofiler 3.6. Eventually, eleven trials (725 participants) were included in the Meta-analyses. There was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in 24 h UTP [RR=-1.23, 95%CI=(-1.94,-0.53), P=0.000 6] or when combining all trials in ALB [RR=3.56, 95%CI=(1.64, 5.47), P=0.000 3]. Meanwhile, there was statistically significant difference between Yiqi Huoxue method and controls when combining all trials in TC [RR=-0.39, 95%CI=(-0.57, -0.20), P<0.000 1] or when combining all trials in TG [RR=-0.49, 95%CI=(-0.82, -0.15), P=0.004]. However, there was no statistically significant difference between Yiqi Huoxue method and controls when combining all trials in Scr [RR=-3.25, 95%CI=(-9.35, 2.84), P=0.30] or when combining all trials in BUN [RR=-0.81,95%CI=(-2.29, 0.66), P=0.28]. In the statistics, the most frequently used Chinese medicines in clinical application were Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma, Codonopsis Radix, Atractylodis Macrocephalae Rhizome and Salvia Miltiorrhiza. The present evidences suggested that Yiqi Huoxue method should be thought highly of in the treatment of IMN, and at the same time, the rational use of traditional Chinese medicine, such as Astragali Radix, Angelicae Sinensis Radix, Chuanxiong Rhizoma also should be paid attention to. However, due to the GRADE evidence grading of the primary outcome measure of 24 h UTP had very low quality, this review can not provide high-quality evidence to prove the clinical efficacy of this method. More well-designed and large-scale multi-center randomized controlled trials should be conducted in the future for verification.

The effects of surface neuromuscular electrical stimulation on post-stroke dysphagia: a systemic review and meta-analysis.

OBJECTIVE: In this study, we intended to evaluate whether swallow treatment with neuromuscular electrical stimulation is superior to that without neuromuscular electrical stimulation, and whether neuromuscular electrical stimulation alone is superior to swallow therapy. METHODS: We searched the PubMed and Scopus databases from their earliest record to 31 December 2014 for randomized and quasi-randomized controlled trials that used neuromuscular electrical stimulation to treat post-stroke dysphagia. The Jadad scale was used to assess the quality of the included studies. We extracted the mean differences and standard deviation (SD) between baseline and posttreatment or posttreatment mean and SD for selected outcomes measured in the experimental and control groups for subsequent meta-analyses. RESULTS: Eight studies were identified. For the comparison "swallow treatment with neuromuscular electrical stimulation vs. swallow treatment without neuromuscular electrical stimulation," we found a significant standardized mean difference (SMD) of 1.27 (95% confidence interval (CI) = 0.51-2.02, P = 0.001) with significant heterogeneity (I(2) = 85%). The meta-analysis for the comparison of neuromuscular electrical stimulation alone and swallow therapy demonstrated a non-significant SMD of 0.25 (95% CI = -0.16-0.65, P = 0.23) without significant heterogeneity (I(2) = 16%). CONCLUSION: Swallow treatment with neuromuscular electrical stimulation seems to be more effective than that without neuromuscular electrical stimulation for post-stroke dysphagia in the short term considering the limited number of studies available. Evidence was insufficient to indicate that neuromuscular electrical stimulation alone was superior to swallow therapy.

Systems biology of meridians, acupoints, and chinese herbs in disease.

Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM). They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.

Arginine-rich intracellular delivery peptides noncovalently transport protein into living cells.

Plasma membranes of plant or animal cells are generally impermeable to peptides or proteins. Many basic peptides have previously been investigated and covalently cross-linked with cargoes for cellular internalization. In the current study, we demonstrate that arginine-rich intracellular delivery (AID) peptides are able to deliver fluorescent proteins or beta-galactosidase enzyme into animal and plant cells, as well as animal tissue. Cellular internalization and transdermal delivery of protein could be mediated by effective and nontoxic AID peptides in a neither fusion protein nor conjugation fashion. Therefore, noncovalent AID peptides may provide a useful strategy to have active proteins function in living cells and tissues in vivo.