Microbial phosphorus-cycling genes in soil under global change.

The ongoing climate change on the Tibetan Plateau, leading to warming and precipitation anomalies, modifies phosphorus (P) cycling in alpine meadow soils. However, the interactions and cascading effects of warming and precipitation changes on the key "extracellular" and "intracellular" P cycling genes (PCGs) of bacteria are largely unknown for these P-limited ecosystems. We used metagenomics to analyze the individual and combined effects of warming and altered precipitation on soil PCGs and P transformation in a manipulation experiment. Warming and increased precipitation raised Olsen-P (bioavailable P, AP) by 13% and 20%, respectively, mainly caused by augmented hydrolysis of organic P compounds (NaOH-Po). The decreased precipitation reduced soil AP by 5.3%. The richness and abundance of the PCGs' community in soils on the cold Tibetan plateau were more sensitive to warming than altered precipitation. The abundance of PCGs and P cycling processes decreased under the influence of individual climate change factors (i.e., warming and altered precipitation alone), except for the warming combined with increased precipitation. Pyruvate metabolism, phosphotransferase system, oxidative phosphorylation, and purine metabolism (all "intracellular" PCG) were closely correlated with P pools under climate change conditions. Specifically, warming recruited bacteria with the phoD and phoX genes, which encode enzymes responsible for phosphoester hydrolysis (extracellular P cycling), strongly accelerated organic P mineralization and so, directly impacted P bioavailability in alpine soil. The interactions between warming and altered precipitation profoundly influenced the PCGs' community and facilitated microbial adaptation to these environmental changes. Warming combined with increased precipitation compensated for the detrimental impacts of the individual climate change factors on PCGs. In conclusion, warming combined with rising precipitation has boosting effect on most P-related functions, leading to the acceleration of P cycling within microbial cells and extracellularly, including mineralization and more available P release for microorganisms and plants in alpine soils.

Rotenone induces hepatotoxicity in rats by activating the mitochondrial pathway of apoptosis.

As a pesticide extracted from plants, rotenone is widely used to control plant pests. In order to explore the safety of rotenone in the environment, we took 60 healthy male SD rats and randomly divided them into rotenone low-dose group, rotenone medium-dose group, rotenone high-dose group, dimethyl sulfoxide group (DMSO), and control group. After 28 days of oral administration, the rat liver tissue ultrastructure, liver function, oxidative stress indexs, mitochondrial function, and apoptosis-related factors were tested to evaluate the hepatotoxicity and toxicological mechanism of rotenone. The results showed that rotenone significantly increased the hepatic index of rats and the activity of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum. Rotenone can reduce the number of endoplasmic reticulum of hepatocyte, concentrate chromatin and make the hepatocyte nuclears irregular. Rotenone weakened the ATP synthesis ability in mitochondria, decreased the activity of ATP enzyme in mitochondria, and increased the mitochondrial membrane potential in the high-dose group. And it induced oxidative stress damage to the mitochondria of rat liver cells. Rotenone can upregulate the expression of pro-apoptotic factors and downregulate the expression of anti-apoptotic factors. These results indicate that oral rotenone in rats induced hepatotoxicity in a dose-dependent manner. The mechanism of rotenone poisoning is that oxidative stress damages organelles of hepatocyte such as mitochondria and endoplasmic reticulum, resulting in their function being weakened or lost, leading to hepatocyte apoptosis.

Electrical Dry Needling Plus Corticosteroid Injection for Osteoarthritis of the Knee: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of electrical dry needling (DN) plus corticosteroid injection (CSI) on pain, physical function, and global change in patients with osteoarthritis of the knee (KOA). DESIGN: A prospective, single-blinded, randomized controlled trial. SETTING: Pain treatment clinic. PARTICIPANTS: Sixty patients with KOA were randomly assigned to the electrical dry needling plus corticosteroid injection (electrical-DN+CSI) group or CSI group. INTERVENTIONS: The CSI group received glucocorticoid injection only once during the trial, and the electrical-DN+CSI group received glucocorticoid injection combined with 4 sessions of electrical-DN. MAIN OUTCOMES MEASURES: The primary outcome was the numerical rating scale at 3 months. The secondary outcomes were the Western Ontario and McMaster Universities Osteoarthritis Index, the time to complete the Timed Up and Go test, and the score of the global rating of change scale at 3 months. A generalized linear mixed-effects model was used to analyze the repeated measurement data. RESULTS: Baseline characteristics and measurements were similar in the 2 groups. The group by time interaction effect was significant for all variables (P<.05). The electrical-DN+CSI group obtained a more significant reduction in pain intensity and more significant improvement in dysfunction than the CSI group at 3 months (P<.05). The median global rating of change score for the CSI group was +3 (somewhat better), and that for the electrical-DN+CSI group was +4 (moderately better). CONCLUSION: Electrical-DN therapy at myofascial trigger points combined with CSI is more effective at alleviating pain, improving dysfunction, and creating global change than CSI alone for patients with KOA. Electrical-DN may be an essential part of treatment for KOA rehabilitation.

Elemene injection as adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV non-small cell lung cancer: A meta-analysis following the PRISMA guidelines.

BACKGROUND: Elemene injection is an anticancer Chinese patent medicine that is widely used for the treatment of advanced lung cancer. Its active ingredients are ß-, γ- and δ-elemene, which are extracted from Curcumaaromatica Salisb. (Curcumawenyujin Y.H. Chen & C. Ling). PURPOSE: To evaluate the effects of Elemene injection as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with stage III/IV non-small cell lung cancer. STUDY DESIGN: A systematic review and meta-analysis of randomized clinical trials (RCTs). MATERIALS AND METHODS: A systematic review and meta-analysis were conducted following the PRISMA (Preferred Reported Items for Systematic Review and Meta-analysis) guidelines. Analyses were performed using Review Manager 5.3, Comprehensive Meta-Analysis 3.0 and Trial Sequential Analysis software. All RCTs comparing Elemene injection combined with PBC vs. PBC alone were selected and assessed for inclusion. The disease control rate (DCR) was defined as the primary endpoint, and the objective Response rate (ORR), survival rate, quality of life (QOL), cellular immune function and toxicities were the secondary outcomes. RESULTS: 15 RCTs recruiting 1,410 patients with stage III/IV NSCLC were included. The methodological quality of most included trials was low to moderate. Compared with PBC alone, Elemene injection plus PBC can improve DCR (RR = 1.23, 95% CI 1.16 to 1.31, p < 0.00001), ORR (RR = 1.62, 95% CI 1.44 to 1.82, p < 0.00001), 1- and 2-year survival rates (RR = 1.33, 95% CI 1.11 to 1.59, p = 0.002; RR = 1.73, 95% CI 1.21 to 2.46, p = 0.002, respectively), QOL (RR = 1.91, 95% CI 1.58 to 2.32, p < 0.00001), CD4+T cell counts (WMD = 10.43, 95% CI 8.25 to 12.62, p < 0.00001), and the CD4+/CD8+ratio (WMD = 0.78, 95% CI 0.42 to 1.14, p < 0.0001) and can reduce severe toxicities by 58% (RR = 0.42, 95% CI 0.34 to 0.52, p < 0.00001). CONCLUSION: Elemene injection is a safe and effective adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV NSCLC. Elemene injection can improve clinical efficacy, enhance cellular immune function and alleviate the toxicity of chemotherapy. High-quality RCTs with significant survival outcomes and longer follow-ups are warranted to confirm the results further.

Dracorhodin perchlorate regulates fibroblast proliferation to promote rat's wound healing.

In recent years, plant-derived extracts are increasing interest from researchers worldwide due to good efficacy and lower side effects. Among the different plant extracts, Dracorhodin perchlorate (DP) is originated from Dragon's blood which has long been used as a natural medicine with various pharmacological activities. In the present study, we have explored the potential regulation of DP on fibroblast proliferation which promotes wound healing both in vitro and in vivo. DP at treatment of 12-24 h significantly induced fibroblast proliferation which is associated with increasing level of phosphorylated-extracellular signal-regulated kinase (ERK). Moreover, if ERK is halted with siRNA, DP cannot induce fibroblast proliferation. In vivo, DP ointment treatment at low- (2.5 µg/mL), medium- (5 µg/mL) and high-(10 µg/mL) doses, rat wounds healed more rapidly compared with the control group. After DP treatment for 7 days, Serpin family H member 1 (SERPINH1) staining confirmed enhanced fibroblast proliferation in the wound tissue. Finally, phosphorylated-ERK in the wound tissue remarkably increased with DP ointment treatment. Therefore, DP may be developed into a potential lead compounds for the treatment of wounds in clinical trials in the near future.

Simultaneous Application of Photothermal Therapy and an Anti-inflammatory Prodrug using Pyrene-Aspirin-Loaded Gold Nanorod Graphitic Nanocapsules.

Photothermal therapy (PTT) has been extensively developed as an effective approach against cancer. However, PTT can trigger inflammatory responses, in turn simulating tumor regeneration and hindering subsequent therapy. A therapeutic strategy was developed to deliver enhanced PTT and simultaneously inhibit PTT-induced inflammatory response. 1-Pyrene methanol was utilize to synthesize the anti-inflammatory prodrug pyrene-aspirin (P-aspirin) with a cleavable ester bond and also facilitate loading the prodrug on gold nanorod (AuNR)-encapsulated graphitic nanocapsule (AuNR@G), a photothermal agent, through π-π interactions. Such AuNR@G-P-aspirin complexes were used for near-infrared laser-triggered photothermal ablation of solid tumor and simultaneous inhibition of PTT-induced inflammation through the release of aspirin in tumor milieu. This strategy showed excellent effects in vitro and in vivo.

A Smart, Photocontrollable Drug Release Nanosystem for Multifunctional Synergistic Cancer Therapy.

Multifunctional synergistic therapy holds promise in biomedical studies and clinical practice. However, strategies aimed at easily integrating the components of such multimodal therapies are needed. Therefore, we herein report a smart drug release nanosystem able to perform photodynamic therapy, photothermal therapy and chemotherapy in a photocontrollable manner. Doxorubicin (DOX), a chemotherapy drug, and 5, 10, 15, 20-tetrakis (1-methylpyridinium-4-yl) porphyrin (TMPyP4), a photosensitizer, were physically intercalated into a DNA assembly immobilized on gold nanorods. The drugs were efficiently delivered to target cells and released under light irradiation, resulting in a synergism that combined phototherapy and chemotherapy for cancer treatment. This smart, photocontrollable drug release nanosystem promises precisely controlled drug release for multifunctional synergistic cancer therapy.

Dracorhodin Perchlorate Accelerates Cutaneous Wound Healing in Wistar Rats.

Dracorhodin perchlorate (DP) is extracted from Dragon's blood, which is widely used in traditional Chinese medicine, especially in wound healing. The aim of this paper is to investigate the influence of DP ointment, which contained DP dissolved in DMSO and mixed with Vaseline, on cutaneous wound healing in Wistar rats. Forty Wistar rats were divided into two groups: control and DP groups. The skin on the back of each rat was punched with two full-thickness wounds and then treated with the corresponding drug. After 3, 7, 10, 14, and 21 days, four rats were sacrificed for immunological, biochemical, and histological analyses. Compared with the control treatment, DP could significantly promote wound closure. Histological and biochemical analyses of the skin biopsies also showed that DP regulated the expression of inflammatory responses by TNF-α and IL-ß and by supporting wound tissue growth and collagen deposition. Western blot revealed that DP could also facilitate the expression of EGF and VEGF proteins. In conclusion, DP promotes wound healing.

Modified Pulsatilla decoction attenuates oxazolone-induced colitis in mice through suppression of inflammation and epithelial barrier disruption.

Inflammatory bowel diseases (IBDs) are chronic inflammatory gastrointestinal disorders caused by a dysregulated mucosal immune response and epithelial barrier disruption. Conventional treatment of IBD is currently limited to overcoming patient symptoms and is often associated with severe adverse effects from the drugs used. Modified Pulsatilla decoction has been used previously to treat ulcerative colitis (UC) in clinical practice in China, however, the underlying mechanism in the treatment of UC remains to be elucidated. In the present study, the efficiency and mechanisms of modified Pulsatilla decoction in the treatment of oxazolone­induced colitis were investigated. Assessment of clinical colitis and histological examination found that the administration of modified Pulsatilla decoction attenuated the severity of oxazolone­induced colitis in mice. Measurement of cytokine concentration, western blotting and reverse transcription­quantitative polymerase chain reaction demonstrated modified Pulsatilla decoction treatment significantly reduced the secretion of pro­inflammatory cytokines and restored alterations in tight junction proteins in the colon tissues. In addition, modified Pulsatilla decoction suppressed the activation of the nuclear factor­κB signaling pathway. Thus, the findings of the present study demonstrated that modified Pulsatilla decoction offers an effective therapeutic approach for the treatment of IBD and revealed the underlying mechanisms of action offered by modified Pulsatilla decoction.

Simultaneous tracking of drug molecules and carriers using aptamer-functionalized fluorescent superstable gold nanorod-carbon nanocapsules during thermo-chemotherapy.

Controlling and monitoring the drug delivery process is critical to its intended therapeutic function. Many nanocarrier systems for drug delivery have been successfully developed. However, biocompatibility, stability, and simultaneously tracing drugs and nanocarriers present significant limitations. Herein, we have fabricated a multifunctional nanocomposite by coating the gold nanorod (AuNR) with a biocompatible, superstable and fluorescent carbon layer, obtaining the AuNR@carbon core-shell nanocapsule. In this system, the carbon shell, originally obtained in aqueous glucose solutions and, therefore, biocompatible in physiological environments, could be simply loaded with cell-specific aptamers and therapeutic molecules through π-π interactions, a useful tool for cancer-targeted cellular imaging and therapy. Moreover, such a stable and intrinsic fluorescence effect of the AuNR@carbon enabled simultaneous tracking of released therapeutic molecules and nanocarriers under thermo-chemotherapy. The AuNR@carbons had high surface areas and stable shells, as well as unique optical and photothermal properties, making them promising nanostructures for biomedical applications.

Cultivation of Chlorella sp. using raw dairy wastewater for nutrient removal and biodiesel production: Characteristics comparison of indoor bench-scale and outdoor pilot-scale cultures.

The biomass productivity and nutrient removal capacity of simultaneous Chlorella sp. cultivation for biodiesel production and nutrient removal in raw dairy wastewater (RDW) in indoor bench-scale and outdoor pilot-scale photobioreactors were compared. Results from the current work show that maximum biomass productivity in indoor bench-scale cultures can reach 260 mg L(-1) day(-1), compared to that of 110 mg L(-1) day(-1) in outdoor pilot-scale cultures. Maximum chemical oxygen demand (COD), total nitrogen (TN), and total phosphorous (TP) removal rate obtained in indoor conditions was 88.38, 38.34, and 2.03 mg L(-1) day(-1), respectively, this compared to 41.31, 6.58, and 2.74 mg L(-1) day(-1), respectively, for outdoor conditions. Finally, dominant fatty acids determined to be C16/C18 in outdoor pilot-scale cultures indicated great potential for scale up of Chlorella sp. cultivation in RDW for high quality biodiesel production coupling with RDW treatment.

Therapeutic efficacy and mechanism of water-soluble extracts of Banxiaxiexin decoction on BALB/c mice with oxazolone-induced colitis.

The aim of the present study was to investigate the therapeutic effects of water-soluble extracts of Banxiaxiexin decoction, a classical traditional Chinese medicine formulation, on BALB/c mice with experimentally induced ulcerative colitis (UC). Water-soluble extracts of Banxiaxiexin decoction were intragastrically administered to BALB/c mice with oxazolone (OXA)-induced colitis. Sulfasalazine (SASP) was administered intragastrically to OXA-treated mice to establish the SASP group (positive control). Following drug administration, the disease activity index (DAI) and the histopathological inflammation score were recorded. In addition, the expression levels of interleukin (IL)-5 and IL-13 mRNA in the colonic tissue were determined by fluorescent quantitative polymerase chain reaction. The DAI and histopathological inflammation score of the model group were significantly greater compared with those of the control group, and the mRNA expression levels of IL-5 and IL-13 in the colonic tissue were also significantly higher in the model group compared with those in the control group. The intragastric administration of water-soluble extracts of Banxiaxiexin decoction significantly lowered the DAI and histopathological inflammation score. The mRNA expression levels of IL-5 and IL-13 in the colonic tissue were also significantly lowered. The therapeutic effect of Banxiaxiexin decoction was found to be comparable to that of SASP. In conclusion, the results from the present study demonstrate that water-soluble extracts of the traditional Chinese medicine formulation Banxiaxiexin decoction have a therapeutic effect on BALB/c mice with OXA-induced colitis.

Catechol-O-methyltransferase polymorphisms do not play a significant role in pain perception in male Chinese Han population.

Polymorphisms in the human catechol-O-methyltransferase (COMT) gene have been widely studied for their role in pain and analgesia. In this study, sensitivity to potassium iontophoresis, visual analog scale measurements for fixed twofold pain threshold stimulation and pain threshold changes induced by transcutaneous electrical acupoint stimulation (TEAS) were assessed in a population of healthy Chinese males. These results were correlated with the alleles of six single nucleotide polymorphisms (SNP) or diplotypes of common haplotypes designated as low pain sensitive, average pain sensitive, and high pain sensitive in the COMT gene of these subjects. Our results reveal that the alleles of each SNP are not significantly correlated with pain perception except for the rs4633 allele in the 2 Hz TEAS session (P < 0.05). In addition, the six diplotypes of COMT haplotypes, which cover 92.5% of the Chinese population, are also not correlated with pain perception. Moreover, there were no significant differences in pain threshold changes induced by 2 and 100 Hz TEAS among the diplotypes of each SNP or the various haplotypes. These results suggest that COMT activity do not play a significant role in pain perception and TEAS-induced analgesia in the Chinese Han male population.

A computational approach to botanical drug design by modeling quantitative composition-activity relationship.

Herbal medicine has been successfully applied in clinical therapeutics throughout the world. Following the concept of quantitative composition-activity relationship, the presented study proposes a computational strategy to predict bioactivity of herbal medicine and design new botanical drug. As a case, the quantitative relationship between chemical composition and decreasing cholesterol effect of Qi-Xue-Bing-Zhi-Fang, a widely used herbal medicine in China, was investigated. Quantitative composition-activity relationship models generated by multiple linear regression, artificial neural networks, and support vector regression exhibited different capabilities of predictive accuracy. Moreover, the proportion of two active components of Qi-Xue-Bing-Zhi-Fang was optimized based on the quantitative composition-activity relationship model to obtain new formulation. Validation experiments showed that the optimized herbal medicine has greater activity. The results indicate that the presented method is an efficient approach to botanical drug design.

A causal relationship discovery-based approach to identifying active components of herbal medicine.

Herbal medicine is widely applied for clinical use in East Asia and other countries. However, unclear correlation between its complex chemical composition and bioactivity prevents its application in the West. In the present study, a stepwise causal adjacent relationship discovery algorithm has been developed to study correlation between composition and bioactivity of herbal medicine and identify active components from the complex mixture. This approach was successfully applied in discovering active constituents from mixed extracts of Radix Salviae miltiorrhizae and Cortex Moutan. Moreover, advantage of the present approach compared with bioassay-guided isolation was demonstrated by its application on a typical herbal drug. The current work offers a new way to virtually screen active components of herbal medicine, and it might be helpful to accelerate the process of new drug discovery from natural products.

A causal discovery approach to identifying active components of herbal medicine.

In the present study, a stepwise causal adjacent relationship discovery (STEPCARD) method has been developed to identify active components of herbal medicine. The combination of two active components had been successfully recognized from a typical Chinese formulation. Animal experiments validated the computational result. It indicates current work might be helpful to accelerate the process of new drug discovery from herbal medicine.

Empirical study on modeling quantitative composition- activity relationships in chinese herbal medicine.

Chinese herbal medicine (CHM) consists of up to hundreds of chemical components, which have complex relationships with their bioactivities. Quantitatively modeling composition-activity relationships playing a crucial role in drug design from CHM. In this paper, principle component regression, partial least square regression and least square support vector machine were used to perform this task and exhibit high predictive precisions.