Whether mindfulness-guided therapy can be a new direction for the rehabilitation of patients with Parkinson's disease: a network meta-analysis of non-pharmacological alternative motor-/sensory-based interventions.

Background: The treatment for Parkinson's disease (PD) consumes a lot of manpower and financial resources. Non-pharmacological alternative motor-/sensory-based interventions are optimized for the rehabilitation of PD patients. Mindfulness-based therapy shows ideal efficacy, but the diversity of the therapy brings difficulties to the selection of clinicians and patients. Methods: Network meta-analysis in the Bayesian framework was used to evaluate the efficacy of non-pharmacological alternative motor-/sensory-based interventions in improving motor and non-motor symptoms in PD patients. Results: A total of 58 studies (2,227 patients) were included. Compared with the non-intervention group, qigong was associated with improved outcomes in the Timed Up and Go (TUG) test (mean difference (MD) -5.54, 95% confidence interval (CI) -8.28 to -2.77), and UPDRS-I (MD -15.50, 95% CI -19.93 to -7.63). Differences between non-pharmacological alternative motor-/sensory-based interventions were not significant for PDQ-39, UPDRS-I, or UPDRS-II; however, qigong was superior to dance (MD -3.91, 95% CI -6.90 to -0.95), Tai Chi (MD -3.54, 95% CI -6.53 to -0.69), acupuncture (MD -6.75, 95% CI -10.86 to -2.70), music (MD -3.91, 95% CI -7.49 to -0.48), and exercise (MD -3.91, 95% CI -6.49 to -1.33) in the TUG test. Conclusion: This network meta-analysis supports mindfulness-based therapy (e.g., qigong, yoga, and Tai Chi) as a preferred non-pharmacological alternative motor-/sensory-based intervention for PD rehabilitation. Systematic review registration: https://inplasy.com/inplasy-2022-10-0109/, INPLASY2022100109.

Levistolide A ameliorates fibrosis in chronic kidney disease via modulating multitarget actions in vitro and in vivo.

AIMS: The increasing incidence of chronic kidney disease (CKD) urgently calls for effective nephroprotective agents. Traditional Chinese Medicine Angelica sinensis and its formula are well known for CKD therapy, but the underlying mechanisms and effective substances of reno-protective effects remain unclear. To this end, we isolated eleven ligustilide dimers (1-11) from A. sinensis and examined the molecular mechanism of their nephroprotective effects. MAIN METHODS: Because of internal RAS playing an important role in CKD, we used renin expression as a target and screened preliminarily for antifibrotic effects of ligustilide dimers (1-11) by constructing a dual luciferase reporter gene in vitro. Furthermore, the reno-protective effects of the ligustilides and their underlying mechanism were investigated in TGF-ß1-stimulated HK-2 cells and 5/6 nephrectomy (Nx) mice. KEY FINDINGS: The ligustilide dimers exhibited anti-fibrotic effects by inhibiting human renin (hREN) promoter activity to decrease renin expression and down-regulate the expression of fibrosis-related factors, including α-SMA, collagen I, and fibronectin in vitro. Levistolide A (LA) and angeolide keto ester (AK) were screened out to identify their ability and underlying mechanism for treating CKD. Experimental validation further indicated that LA or AK treatment inhibited the expression of key molecules in RAS, TGF-ß1/Smad, and MAPK pathways to downregulate ECM deposition. Furthermore, LA obviously meliorated renal injury in 5/6 Nx mice through ameliorating oxidant stress, inflammation, apoptosis and renal fibrosis. SIGNIFICANCE: The experimental results demonstrated that ligustilide dimers were potential nephroprotective agents. LA might be an attractive drug candidate for renin-targeted CKD therapy.

Ansofaxine hydrochloride inhibits tumor growth and enhances Anti-TNFR2 in murine colon cancer model.

Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy. Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0-50 µM), ansofaxine hydrochloride (0-50 µM) and amitifadine hydrochloride (0-150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA. Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function. Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.

Efficacy of acupuncture in animal models of vascular dementia: A systematic review and network meta-analysis.

Background and purpose: Acupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study. Methods: To analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed. Results: Forty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: -23.41; 95%CI: -26.66, -20.15; I2 = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: -25.87; 95%CI: -30.75, -21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative. Conclusions: Acupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters. Systematic review registration: https://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.

Huogu injection alleviates SONFH by regulating adipogenic differentiation of BMSCs via targeting the miR-34c-5p/MDM4 pathway.

Although the precise pathogenesis of steroid-induced osteonecrosis of femoral head (SONFH) is not yet fully understood, evidence shows miRNAs-mediated posttranscription control directs the adipogenesis of bone marrow mesenchymal stem cells (BMSCs) and plays a pivotal role in the SONFH processes. Huogu injection formulated according to traditional Chinese medicine (TCM) theory has been used to treat SONFH by intra-articular injection. In this study, we asked whether the therapeutic effects of Huogu injection might depend on the inhibition of adipogenic differentiation of BMSCs, and if so, the pathway might be a therapeutic target to promote bone repair. Consequently, miR-34c-5p was upregulated in the dexamethasone (DEX)-treated BMSCs and might participate in the adipogenesis of BMSCs. TargetScan database and the luciferase reporter assay showed miR-34c-5p targeted on the MDM4 and negatively regulated its expression. Huogu injection in vitro inhibited the adipogenesis in the DEX-treated BMSCs by inhibiting the expression levels of PPARγ and C/EBPα, as well as reducing miR-34c-5p to prevent the degradation of MDM4. Moreover, miR-34c-5p mimic or MDM4 knockdown using shRNA neutralized the anti-adipogenesis of Huogu injection in BMSCs. In vivo, the results of X-ray imaging confirmed that Huogu injection alleviated the bone loss in rat SONFH. Consistent with results in vitro, Huogu injection reduced the lipid accumulation, removed the suppression of MDM4 by downregulating the expression of miR-34c-5p, and inhibited the expression of C/EBPα and PPARγ in bone tissues. When the lentivirus encoding miR-34c-5p was conducted by intra-articular injection, the overexpression of miR-34c-5p antagonized the therapeutic effects of Huogu injection. Our results underline the critical importance of the miR-34c-5p/MDM4 pathway in regulating the adipogenic outcome of BMSCs, suggesting the miR-34c-5p as a potentially effective therapeutic target in SONFH. These results further reinforce the potential of Huogu injection as an alternative approach in SONFH.

Effect of Electro-Acupuncture on Lateralization of the Human Swallowing Motor Cortex Excitability by Navigation-Transcranial Magnetic Stimulation-Electromyography.

Background: The use of transcranial magnetic stimulation combined with electromyography for the functional evaluation of the cerebral cortex in both clinical and non-clinical populations is becoming increasingly common. Numerous studies have shown that electro-acupuncture (EA) can regulate cerebral cortical excitability. However, the effect of EA on the lateralization of the human swallowing motor cortex excitability is not yet fully understood. Objective: The aim of this study was to assess whether lateralization is present in the swallowing motor cortex of healthy subjects, and to investigate the impact of EA at Lianquan (CV23) and Fengfu (GV16) on lateralization. Methods: Forty subjects were randomized 1:1 into the EA group and the sham-EA group. The bilateral swallowing motor cortices was located by a neuroimaging navigation system. Then, the resting motor threshold (RMT) and motor evoked potential (MEP) of the mylohyoid of healthy subjects were recorded while applying combined transcranial magnetic stimulation and electromyography before and after EA or sham-EA. Results: First, the RMT and MEP latency of the contralateral mylohyoid innervated by the right swallowing cortex (71.50 ± 1.67%, 8.30 ± 0.06 ms) were lower than those innervated by the left (79.38 ± 1.27%, 8.40 ± 0.06 ms). Second, EA at CV23 and GV16 reduced the bilateral RMT and enhanced the bilateral MEP latency and amplitude (P = 0.005, P < 0.001; P = 0.002, P = 0.001; P = 0.002, P = 0.009), while sham-EA did not (P > 0.05). Third, EA had an effect on the RMT and MEP latency in terms of lateralization changes, but this was not significant (P = 0.067, P = 0.156). Conclusion: The right swallowing motor cortex of healthy subjects is more excitable than that of the left at resting state. Thus, we found that lateralization is present in the swallowing motor cortex of healthy people, which might indicate a hemispheric dominance of swallowing predominates in the right swallowing motor cortex. In addition, EA at CV23 and GV16 can instantly promote the excitability of the bilateral swallowing motor cortices. But there was no significant difference in EA stimulation in terms of lateralization.

Influence of persulfate on transformation of phosphorus and heavy metals for improving sewage sludge dewaterability by hydrothermal treatment.

Activated persulfate oxidation has been proven to be an efficient advanced sludge treatment technique to improve sludge dewaterability. This study investigates the influence of persulfate on the transformation of phosphorus (P) and heavy metals (HMs) during the hydrothermal treatment of sewage sludge. The hydrothermal temperature, time, and persulfate concentration are optimized by a Box-Behnken design to obtain the best sludge dewaterability, which is expressed by capillary suction time (CST). The highest CST reduction efficiency is 90.5% at the optimal hydrothermal temperature, time, and concentration of persulfate, which are 145 °C, 2 h, and 150 mg/g dry sludge (DS), respectively. The distribution and transformation of P and HMs with different persulfate concentrations (100-200 mg/g DS) during the hydrothermal process are investigated. Results show that more than 90% of the P and HMs in the sludge are retained in sludge cakes after the hydrothermal treatment. The addition of SPS can make the P in the sludge cakes transform into more stable P species according to the extraction capacity of sequential extracts. It can be found from the ecological risk indexes of the HMs that the addition of SPS during the hydrothermal treatment of sludge can reduce the environmental risk of HMs. This study provides insights into the P and HM distribution and transformation during hydrothermal treatment with persulfate, providing a reference for sludge recovery strategies.

Bipolar transurethral enucleation of the prostate combined with open cystolithotomy in the treatment of large and giant prostate with bladder stones: Case series.

The surgical management of large or giant prostate still has challenges to urologists, especially if combined with bladder stones, and the traditional techniques by open prostatectomy and cystolithotomy have significant morbidity rates. The endoscopic procedure might not be feasible to treat both conditions in a single procedure, despite advances in surgical techniques and instrumentation, we present a one-session procedure by a combined endoscopic and open approach for treating benign prostatic hyperplasia (BPH) larger than 100 g combined with bladder stones in the elderly patient with other comorbidities. Between May 2017 and January 2020, bipolar transurethral plasma kinetic enucleation of the prostate (TUEP) followed by open cystolithotomy was performed to six patients at our institution, three of them combined with a big bladder stone(s). All the patients have other chronic chest and heart diseases; we retrospectively collected the data. All the patients diagnosed as BPH of big size or giant prostate over 100 g, with bladder stone, and all the patients treated with the same procedure. We founded that the combination methods showed a significant effect in terms of surgery time, patient outcomes and recovery, hospital discharge. The mean age of patients was 78.16 ± 4.2 (73-84) years, and the mean prostate-specific antigen (PSA) value was 16.27 ± 10.01 (8.32-32.17) ng/mL. The mean size of the prostate measured by MRI/US was 266.16 ± 89.1 (169-405) mL. The mean total operation time was 70.5 ± 10.9 (60-90) min, while the mean enucleation time was 28.38 ± 6.61 (23-40) min. The mean intraoperative blood loss was 193.33 ± 19.66 (170-220) mL. The mean resected prostate weight was 217.166 ± 94.67 (117-365) g. The mean post-operative hospital stay was 2.6 ± 0.81 (2-4) days. One patient was readmitted 2 months later due to urinary tract infection, and one patient complains of urine incontinence who spontaneously subsided in 4 months after surgery, other that no severe postoperative complications observed, a significant reduction of serum PSA and IPSS recorded at 3 months, postoperatively. Although simple open prostatectomy remains the reference standard for the treatment. Of excessively large or giant prostatic hyperplasia, the combination procedure not only facilitates the management of selected cases of hyperplasia but further imparts significant benefits to patients and surgeons alike. This treatment plan is safe, time-consuming, and could revolutionize future treatment approaches to giant prostate.

Oridonin Dose-Dependently Modulates the Cell Senescence and Apoptosis of Gastric Cancer Cells.

Gastric cancer (GC) is the fourth most lethal cancer. Effective treatments are lacking, and our knowledge of the pathogenic mechanisms in play is poor. Oridonin from the Chinese herb Rabdosia rubescens exerts various anticancer activities. However, the dose-dependent effects of oridonin on human GC remain unclear. Here, we found that oridonin inhibited GC cell growth in a time- and dose-dependent manner. Low-dose oridonin induced GC cell cycle arrest at G0/G1 and cell senescence by suppressing the c-Myc-AP4 pathway and enhancing p53-p21 signaling. AP4 overexpression partly abrogated the oridonin-induced senescence of GC cells. High-dose oridonin induced apoptosis and autophagy, with the autophagy inhibitor BafA1 attenuating oridonin-induced apoptosis. Together, the findings indicate that oridonin at different doses modulates GC cell senescence and apoptosis; oridonin may thus usefully treat GC.

Influence of rice husk addition on phosphorus fractions and heavy metals risk of biochar derived from sewage sludge.

This study investigated the effects of rice husk dose and pyrolysis temperature on the phosphorus (P) fractions and environmental risk of heavy metals in biochar co-pyrolyzed from sewage sludge and rice husk. Biochar properties were analyzed, and the transformation of P and heavy metals speciation during co-pyrolysis were also discussed. Co-pyrolysis of raw sludge and rice husk (10-50 wt%) could increase the carbonization degree and stability of biochar at 500 °C. The organic P (OP) in raw sludge (68 wt%) was transformed to inorganic P (IP) during co-pyrolysis, indicating that the addition of rice husk could improve biochar-P bioavailability by promoting the transformation of IP. The IP content increased from 71.5 wt% of sludge biochar to 92 wt% of blended biochar (50 wt% sludge and 50 wt% rice husk) at a pyrolysis temperature of 500 °C. With the mass ratio of sludge to rice husk of 5:5, the OP content decreased from 3 mg g-1 to 0.75 mg g-1 as the pyrolysis temperature increased from 300 °C to 700 °C. The 31P nuclear magnetic resonance spectra and X-ray photoelectron spectroscopy results showed that P species in biochar mainly existed as orthophosphate, which can be directly taken up by plants. After co-pyrolysis, the toxicity and mobility of heavy metals gradually decreased with increasing rice husk dose and pyrolysis temperature. The study indicates that co-pyrolysis of sewage sludge and rice husk could be a promising P reuse strategy.

p-MEK expression predicts prognosis of patients with adenocarcinoma of esophagogastric junction (AEG) and plays a role in anti-AEG efficacy of Huaier.

The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) is increasing worldwide with poor prognosis and unclear pathogenesis. Trametes robiniophila Murr. (Huaier), a traditional Chinese medicine has been used in the clinical treatment of a variety of solid tumors, including AEG. However, its anticancer components and molecular mechanisms are still unclear. In our previous studies, we have found that Huaier n-butanol extract (HBE) shows the most potent anticancer activity among different extracts. In the present study, we aimed to investigate the clinical relevance of p-MEK expression in AEG patients and the role of the MEK/ERK signaling pathway in the anti-AEG efficacy of HBE in vitro and in vivo. We herein demonstrate that p-MEK expression in AEG tissues was significantly higher than that in paracancerous tissues and correlated with a poor prognosis in AEG patients. We further found that HBE inhibited the colony formation, migration, and invasion in AEG cell lines in a concentration-dependent manner in vitro. HBE also suppressed the growth of AEG xenograft tumors without causing any host toxicity in vivo. Mechanistically, HBE caused the inactivation of the MEK/ERK signaling pathway by dephosphorylating MEK1 at S298, ERK1 at T202, and ERK2 at T185 and modulating the expression of EMT-related proteins. In summary, our results demonstrate that the high expression of p-MEK may be an independent factor of poor prognosis in patients with AEG. The clinically used anticancer drug Huaier may exert its anti-AEG efficacy by inhibiting the MEK/ERK signaling pathway.

Physalis alkekengi var. franchetii Extracts Exert Antitumor Effects on Non-Small Cell Lung Cancer and Multiple Myeloma by Inhibiting STAT3 Signaling.

BACKGROUND: Physalis alkekengi var. franchetii is an herb that possesses various ethnopharmacological applications. Herein, our current study focuses on the antitumor effect of a combination of physalins, which are regarded as the most representative secondary metabolites from calyces of Physalis alkekengi var. franchetii. MATERIALS AND METHODS: We mainly investigated the antitumor activity of the physalins extracted from Physalis alkekengi var. franchetii on both solid and hematologic cancers. The main cells used in this study were NCI-H1975 and U266 cells. The major assays used were the CCK-8 assay, Western blot analyses, immunofluorescence assay and Annexin V assay, and a xenograft mouse model was used. RESULTS: The results showed that physalins exhibited a strong antitumoural effect on both non-small cell lung cancer (NSCLC) and multiple myeloma (MM) cells by suppressing constitutive STAT3 activity and further inhibiting the downstream target gene expression induced by STAT3 signaling, which resulted in the enhanced apoptosis of tumor cells. Moreover, physalins significantly reduced tumor growth in xenograft models of lung cancer. CONCLUSION: Collectively, these findings demonstrated that the physalins from Physalis alkekengi var. franchetii may potentially act as cancer preventive or chemotherapeutic agents for NSCLC and MM by inhibiting the STAT3 signaling pathway. The present study served as a promising guide to further explore the precise mechanism of Physalis alkekengi var. franchetii in cancer treatment.

Tanshinone I Mitigates Steroid-Induced Osteonecrosis of the Femoral Head and Activates the Nrf2 Signaling Pathway in Rats.

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 µg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.

Synergistic Effect and Mechanism of Plumbagin with Gentamicin Against Carbapenem-Resistant Klebsiella pneumoniae.

BACKGROUND: Aminoglycosides are one of a few susceptible antimicrobials available for carbapenem-resistant Enterobacteriaceae (CRE). However, the altered pharmacokinetics and increasing drug resistance of aminoglycosides will make them hardly effective if used in monotherapy. The purpose of this study was to identify herbal compounds that potentiate the antibacterial effect of gentamicin against carbapenem-resistant Klebsiella pneumoniae (CRKp) with gentamicin resistance and explore the action mechanisms. METHODS: A collection of 280 Chinese herbal compounds was screened for synergistic effect with gentamicin against CRKp by broth microdilution method according to the standard of the Clinical and Laboratory Standards Institute (CLSI). Intracellular gentamicin was measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The membrane potential was evaluated by BacLightTM Bacterial Membrane Potential Kit. Plumbagin-induced metabolite changes of vital metabolic pathways were measured by an optimized untargeted metabolomics method based on gas chromatography-mass spectrometer (GC/MS). Intracellular nicotinamide adenine dinucleotide (NADH) was detected via EnzyChrom NAD/NADH assay kit. RESULTS: We identified plumbagin to remarkably potentiate the antimicrobial activity of gentamicin against the CRKp with gentamicin resistance. Plumbagin at 100 µM could bring the MIC of gentamicin from >16 µg/mL to ~4 µg/mL despite its minimal inhibitory effect on the CRKp. A similar synergistic effect with gentamicin was also observed in an antibiotics-susceptible strain of Klebsiella pneumoniae. Compared with gentamicin monotreatment, the combination group showed a higher intracellular concentration of gentamicin and increased membrane potential in CRKp. Metabolomics analysis indicated remarkable increases of malate and α-ketoglutarate in the tricarboxylic acid (TCA) cycle in the CRKp upon plumbagin treatment. Further analysis revealed higher intracellular NADH concentration in plumbagin-treated CRKp, supporting increased proton-motive force (PMF) that facilitates aminoglycosides uptake. CONCLUSION: Herbal compound plumbagin was identified to stimulate gentamicin uptake by CRKp via enhancing TCA efflux and PMF to achieve a synergistic antibacterial effect. Plumbagin may be used in combination with aminoglycosides for severe CRKp infection by potentiating their therapeutic efficacy and lowering dosage.

Enhanced electrochemical phosphate recovery from livestock wastewater by adjusting pH with plant ash.

In the field of environmental wastewater treatment, it is a very meaningful topic to recover phosphate from swine wastewater in the form of struvite precipitation. The solution pH is one of the important influencing factors in the process of struvite precipitation. In this paper, an attempt was made to recover the phosphate from swine wastewater by adding plant ash. Experimental results have revealed that aeration can be replaced by optimal plant ash adding mode to increase the phosphate recovery efficiency. With the dosages of plant ash and magnesium metal were respectively 11.66 and 3.33 g/L the phosphate recovery efficiency reached 97.69% in 60 min. The efficiency was still above 95% after repeatedly using magnesium pellet for 3 times. The economic evaluation further revealed that the recovery cost of the proposed method was 0.62 $/kg PO4-P.

Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption.

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6'-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS's absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

Triptolide enhances chemotherapeutic efficacy of antitumor drugs in non-small-cell lung cancer cells by inhibiting Nrf2-ARE activity.

Non-small cell lung cancer (NSCLC) has a high mortality rate worldwide. Various treatments strategies have been used against NSCLC including individualized chemotherapies, but innate or acquired cancer cell drug resistance remains a major obstacle. Recent studies revealed that the Kelch-like ECH associated protein 1/Nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2) pathway is intimately involved in cancer progression and chemoresistance. Thus, antagonizing Nrf2 would seem to be a viable strategy in cancer therapy. In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various cancer cells, including NSCLC and liver cancer cells. Consequently, triptolide made cancer cells more chemosensitivity toward antitumor drugs both in vitro and in a xenograft tumor model system using lung carcinoma cells. These results suggest that triptolide blocks chemoresistance in cancer cells by targeting the Nrf2 pathway. Triptolide should be further investigated in clinical cancer trials.

Effectiveness and mechanism of natural attenuation at a petroleum-hydrocarbon contaminated site.

This study applied an integrated method for evaluating the effectiveness and mechanism of natural attenuation (NA) of petroleum-hydrocarbon contaminated groundwater. Site groundwater and soil samples were analysed to characterize spatial and temporal variations in petroleum hydrocarbons, geochemical indicators, microbial diversity and isotopes. The results showed that the area of petroleum hydrocarbon contamination plume decreased almost 60% in four years, indicating the presence of natural attenuation. The 14C content and sequence analysis indicate that there are more relatively 'old' HCO3- that have been produced from petroleum hydrocarbons in the upgradient portion of the contaminated plume, confirming that intrinsic biodegradation was the major factor limiting spread of the contaminated plume. The main degradation mechanisms were identified as sulfate reduction and methanogenesis based on the following: (1) more SO42- have been consumed in the contamination source than downgradient, and the δ34S values in the resident SO42- were also more enriched in the contamination source, (2) production of more CH4 in the contamination source with the δ13C values for CH4 was much lower than that of CO2, and the fractionation factor was 1.030-1.046. The results of this study provide significant insight for applying natural attenuation and enhanced bioremediation as alternative options for remediation of petroleum-hydrocarbon contaminated sites.

Danshen attenuates cartilage injuries in osteoarthritis in vivo and in vitro by activating JAK2/STAT3 and AKT pathways.

Articular cartilage degradation is a main feature of osteoarthritis (OA). The effects of Danshen, a traditional Chinese herb, in mitigating cartilage damage have been reported before. This study was conducted to investigate the effects of Danshen on cartilage injuries in OA. Rabbit OA models were established by surgical destabilization of the medial meniscus and the anterior and posterior cruciate ligaments in the left knee joint. Injection of Danshen into the articular cavity attenuated OA cartilage destruction in vivo. The levels of phosphorylated Janus kinase 2 (JAK2) and phosphorylated signal transducer and activator of transcription 3 (STAT3) were decreased in osteoarthritic cartilage, while they were rescued upon Danshen treatment. Furthermore, chondrocytes isolated from normal rabbit cartilage were exposed to 2 mM sodium nitroprusside (SNP) to establish an OA model in vitro. We found that the oxidative stress and chondrocyte apoptosis induced by SNP were suppressed by Danshen. The phosphorylation levels of JAK2 and STAT3 were decreased in response to SNP treatment, whereas they were rescued by Danshen. Additionally, AG490, a specific JAK2 inhibitor, counteracted the anti-apoptotic effect of Danshen. The phosphorylation level of protein kinase B (AKT) was also altered in response to SNP and reversed by Danshen. The anti-apoptotic effect of Danshen was counteracted by AKT pathway inhibitor LY194002. Taken together, Danshen attenuates OA cartilage destruction by regulating the JAK2/STAT3 and AKT signaling pathways.

Danshen attenuates osteoarthritis-related cartilage degeneration through inhibition of NF-κB signaling pathway in vivo and in vitro.

Danshen (Salvia miltiorrhiza) is a traditional Chinese medicine herb that can alleviate the symptoms of osteoarthritis (OA) (Söder et al. 2006) in animals. However, the underlying mechanisms remain poorly understood and require further investigation. In this study, rabbits with experimentally induced OA were given an intra-articular injection of danshen (0.7 mL/day) for 5 weeks. In addition to attenuating the cartilage degeneration of OA in the rabbits, danshen decreased the expression and activity of matrix metalloproteinase 9 (MMP-9) and MMP-13, and increased the expression of their natural inhibitors: tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and TIMP-2. Apoptosis in osteoarthritic cartilage tissues was attenuated by danshen, accompanied with increased expression of B cell lymphoma 2 (Bcl-2) and decreased levels of Bcl-2-associated X protein (Bax). Further, danshen inhibited the nuclear accumulation of nuclear factor kappa-B (NF-κB) p65 in osteoarthritic cartilage. The therapeutic effects of danshen in vivo were comparable to that of sodium hyaluronate, which is a drug used clinically for the treatment OA. In vitro, sodium nitroprusside (SNP) was used to stimulate apoptosis in primary rabbit chondrocytes. We found that the SNP-induced apoptosis was mitigated by danshen. BAY11-7028, an inhibitor of the NF-κB pathway, augmented danshen's anti-apoptotic effects in cells exposed to SNP. When these results are considered together, they indicate that danshen alleviates the cartilage injury in rabbit OA through inhibition of the NF-κB signaling pathway.