Aucubin Promotes Osteogenic Differentiation and Facilitates Bone Formation through the lncRNA-H19 Driven Wnt/ß-Catenin Signaling Regulatory Axis.

Objectives: Traditional Chinese medicine Cortex Eucommiae has been used to treat bone fracture for hundreds of years, which exerts a significant improvement in fracture healing. Aucubin, a derivative isolated from Cortex Eucommiae, has been demonstrated to possess anti-inflammatory, immunoregulatory, and antioxidative potential. In the present study, our aim was to explore its function in bone regeneration and elucidate the underlying mechanism. Materials and Methods: The effects of Aucubin on osteoblast and osteoclast were examined in mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) and RAW 264.7 cells, respectively. Moreover, the lncRNA H19 and Wnt/ß-catenin signaling were detected by qPCR examination, western blotting, and luciferase activity assays. Using the femur fracture mice model, the in vivo effect of Aucubin on bone formation was monitored by X-ray, micro-CT, histomorphometry, and immunohistochemistry staining. Results: In the present study, Aucubin was found to significantly promote osteogenic differentiation in vitro and stimulated bone formation in vivo. Regarding to the underlying mechanism, H19 was found to be obviously upregulated by Aucubin in MSCs and thus induced the activation of Wnt/ß-catenin signaling. Moreover, H19 knockdown partially reversed the Aucubin-induced osteogenic differentiation and successfully suppressed the activation of Wnt/ß-catenin signaling. We therefore suggested that Aucubin induced the activation of Wnt/ß-catenin signaling through promoting H19 expression. Conclusion: Our results demonstrated that Aucubin promoted osteogenesis in vitro and facilitated fracture healing in vivo through the H19-Wnt/ß-catenin regulatory axis.

Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis.

BACKGROUP: Currently, aromatherapy is being increasingly utilized in clinical practice, particularly in managing the side effects associated with radiotherapy and chemoradiotherapy. However, it remains to be established whether aromatherapy can effectively alleviate these symptoms. OBJECTIVE: To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and chemotherapy. METHODS: Seven databases were researched from inception until September 29, 2023, including PubMed, Scopus, and Web of Science, Chinese National Knowledge Infrastructure, Wanfang database, China Biology Medicine disc and VIP Chinese Medical Journal Database. Review Manager version 5.3 was utilized for data analysis. The Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the study. Evidence quality rating was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach through the GRADEpro GDT online tool. RESULTS: Nineteen studies involving 1,541 patients were included. Aromatherapy can alleviate nausea [relative risk (RR)=0.64, 95% confidence interval (CI): 0.53 to 0.78, P<0.05, I2=46%; standardized mean difference (SMD)=-0.86, 95% CI: -1.21 to -0.51, P<0.05, I2=64%] and vomiting (RR=0.54, 95% CI: 0.42 to 0.69, P<0.05, I2=35%; SMD=-1.28, 95% CI: -1.52 to -1.03, P<0.05, I2=92%), improve sleep disorders [mean difference (MD)=-3.39, 95% CI: -3.95 to -2.84, P<0.05, I2=0%], relieve pain (SMD=-1.58, 95% CI: -1.96 to -1.21, P<0.05, I2=0%), mitigate fatigue (SMD=-1.28, 95% CI: -2.44 to -0.11, P<0.05, I2=93%) and enhance quality of life (SMD=0.50, 95% CI: 0.22 to 0.79, P<0.05, I2=0%) in cancer patients after radiotherapy and chemotherapy, but it may not have a significant effect on anxiety. The risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2, and no studies were considered to be of high grade according to the GRADE system. CONCLUSIONS: Aromatherapy is an efficacious, safe and economic adjunctive therapy for cancer patients, which can mend the physical symptoms and mental health of cancer patients. However, more high-quality studies are needed to verify it. (PROSPERO registration No. CRD42023390171).

Baicalin induces ferroptosis in osteosarcomas through a novel Nrf2/xCT/GPX4 regulatory axis.

BACKGROUND: Osteosarcomas (OS) is a kind of malignant bone tumor which occurs primarily in children and adolescents, and the clinical therapeutics remain disappointing. As a new programmed cell death, ferroptosis is characterized by iron dependent and intracellular oxidative accumulation, which provides a potential alternative intervene for the OS treatment. Baicalin, a major bioactive flavone derived from traditional Chinese medicine Scutellaria baicalensis, has been proved to have anti-tumor properties in OS. Whether ferroptosis participated in the baicalin mediated anti-OS activity is an interesting project. PURPOSE: To explore the pro-ferroptosis effect and mechanisms of baicalin in OS. METHODS/STUDY DESIGN: Pro-ferroptosis effect of baicalin on cell death, cell proliferation, iron accumulation, lipid peroxidation production was determined in MG63 and 143B cells. The levels of glutathione (GSH), oxidized (GSSG) glutathione and malondialdehyde (MDA) were determined by enzyme linked immunosorbent assay (ELISA). The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Glutathione peroxidase 4 (GPX4) and xCT were detected by western blot in baicalin-mediated ferroptosis regulation. In vivo, a xenograft mice model was adopted to explore the anticancer effect of baicalin. RESULTS: In the present study, it was found that baicalin significantly suppress tumor cell growth in vitro and in vivo. By promoting the Fe accumulation, ROS formation, MDA production and suppressing the ratio of GSH/GSSG, baicalin was found to trigger ferroptosis in OS and ferroptosis inhibitor ferrostatin-1 (Fer-1) successfully reversed these suppressive effects, indicating that ferroptosis participated in the baicalin mediated anti-OS activity. Mechanistically, baicalin physically interacted with Nrf2, a critical regulator of ferroptosis, and influenced its stability via inducing ubiquitin degradation, which suppressed the Nrf2 downstream targets GPX4 and xCT expression, and led to stimulating ferroptosis. CONCLUSIONS: Our findings for the first time indicated that baicalin exerted anti-OS activity through a novel Nrf2/xCT/GPX4-dependent ferroptosis regulatory axis, which hopefully provides a promising candidate for OS treatment.

Characterization of microbial community, ecological functions and antibiotic resistance in estuarine plastisphere.

The plastisphere is a new ecological niche. Compared to the surrounding water, microbial community composition associated with the plastisphere is known to differ with functional consequences. Here, this study characterized the bacterial and fungal communities associated with four types of plastisphere (polyethylene, polystyrene, polypropylene and polyvinyl chloride) in an estuarine habitat; assessed ecological functions including carbon, nitrogen, phosphorus and sulfur cycling, and determined the presence of antibiotic resistance genes (ARGs) and human pathogens. Stochastic processes dominated the community assembly of microorganisms on the plastisphere. Several functional genera related to nutrient cycling were enriched in the plastisphere. Compared to surrounding water and other plastisphere, the abundances of carbon, nitrogen and phosphorus cycling genes (cdaR, nosZ and chpy etc.) and ARGs (aadA2-1, cfa and catB8 etc.) were significantly increased in polyvinyl chloride plastisphere. In contrast, the polystyrene plastisphere was the preferred substrate for several pathogens being enriched with for example, Giardia lamblia 18S rRNA, Klebsiella pneumoniae phoE and Legionella spp. 23S rRNA. Overall, this study showed that different plastisphere had different effects on ecological functions and health risk in estuaries and emphasizes the importance of controlling plastic pollution in estuaries. Data from this study support global policy drivers that seek to reduce plastic pollution and offer insights into ecological functions in a new ecological niche of the Anthropocene.

Immediate Effects of Acupuncture on Explosive Force Production and Stiffness in Male Knee Joint.

Acupuncture can improve explosive force production and affect joint stiffness by affecting muscle activation levels. This study aims to explore the effects of true acupuncture (TA) compared with sham acupuncture (SA) on the explosive force production and stiffness of the knee joint in healthy male subjects. Twenty subjects were randomly divided into the TA group (n = 10) and SA group (n = 10) to complete isokinetic movement of the right knee joint at a speed of 240°/s before and after acupuncture. Futu (ST32), Liangqiu (ST34), Zusanli (ST36), Xuehai (SP10), and Chengshan (BL57) were selected for acupuncture. The intervention of SA is that needles with a blunt tip were pushed against the skin, giving an illusion of insertion. The results showed that acupuncture and the intervention time had a significant interaction effect on knee joint explosive force and joint stiffness (p < 0.05). The average maximum (max) torque, average work, average power, average peak power and total work of the TA group increased significantly after acupuncture (p < 0.05), while the SA group did not (p > 0.05). Therefore, true acupuncture can immediately improve the explosive force and joint stiffness of the male knee joint by inducing post-activation potentiation (PAP) and/or De-Qi.

Effects of Traditional Chinese Acupuncture Compared with Sham Acupuncture on the Explosive Force Production by the Forearm Muscles in Female: A Randomized Controlled Trial.

BACKGROUND: Acupuncture can effectively enhance musculoskeletal rehabilitation, with effects such as reduced pain intensity and muscle tension and decreased disability. OBJECTIVE: The purpose of this study was to determine the efficacy of traditional Chinese acupuncture (TCA) compared with sham acupuncture (SA) in explosive force production by the forearm muscles in females. METHODS: A total of 32 subjects were included and randomly assigned to two groups: TCA group (n = 16): stimulated specific acupoints including Quchi (LI11), Shousanli (LI10), Hegu (LI4), Xiaohai (SI8), Tianjing (SJ10), and Waiguan (SJ5) for 15 minutes; SA group (n = 16): using superficial needle insertion at nonacupoints without stimulation. The subjects warmed up for the 3-time isokinetic test with an angular velocity of 30°/s and then performed a set of 15 full flexion (Flex) and extension (Ext) with an angular velocity of 180°/s using the CON-TREX isokinetic test training system recorded as the pretest. After acupuncture for 15 min, perform a set of the same isokinetic movement isokinetic records as the posttest. The average max torque, average work, average power, average peak power, average max speed, and total work were collected to evaluate the forearm explosive force changes. Use two-way repeated measures ANOVA to compare the difference before and after acupuncture between two groups. RESULTS: The results showed that acupuncture conditions (sham acupuncture as well as true acupuncture) and the intervention times (not acupuncture or acupuncture for 15 min) have a significant interaction effect on forearm explosive force and joint stiffness (P < 0.05). The simple main effect showed that the selected parameters of the TCA group increased significantly after acupuncture (P < 0.05), while the SA group did not (P > 0.05). We speculate that the activation of muscle may be related to the selected acupuncture points. CONCLUSION: Acupuncture can produce excitation in motor nerves and muscles, and nerve stimulation increases the recruitment of motor units, thus improving the muscle explosive force.

Effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus: A protocol for systematic review and meta analysis.

BACKGROUND: There is limited study that has conducted a review investigating the clinical effects of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with gestational diabetes mellitus (GDM). Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we undertook a systematic review and meta-analysis to assess the effectiveness and safety of vitamin and omega-3 fatty acid co-supplementation on blood glucose in women with GDM. METHODS: This protocol was written following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) statement guidelines. We will conduct systematic reviews and meta-analyses to identify relevant randomized controlled trials (RCTs) involving vitamin and omega-3 fatty acid co-supplementation on GDM in electronic databases including PubMed, Web of Science, Embase, and the Cochrane Library up to June 2021. Exclusion criteria include observational studies, non-RCTs, review articles, studies with a sample size <50, and studies with insufficient outcome data. The primary outcomes include fasting glucose and insulin. Secondary outcomes are evaluated in a homeostasis model of insulin resistance, total antioxidant capacity, triglycerides, total cholesterol, low-density lipoprotein cholesterol, preterm birth and macrosomia over 4 kg. RESULTS: The review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings. REGISTRATION NUMBER: 10.17605/OSF.IO/NSW54.

Six weeks of Jilin ginseng root supplementation attenuates drop jump-related muscle injury markers in healthy female college students.

BACKGROUND: Eccentric muscle contraction is an inherent component of numerous sporting movements but can result in muscle fatigue and injury, especially when engaging in unfamiliar exercise, which requires pharmacological intervention. Jilin ginseng root (GS) has been used to protect muscles and reduce the risk of exercise injury. AIM OF THE STUDY: In this study, we sought to examine and demonstrate the effectiveness of using GS in preventing muscle stiffness and reducing the risk of exercise injury in women. METHODS: Twenty females were randomly assigned to GS and placebo groups. Body composition, serum biochemistry index, kinematics, and endurance exercise tests were measured at two time point presupplementation and 6 weeks after supplementation. The major compounds of GS were characterized using a high-performance liquid chromatograph with a gradient delivery system (HPLC). RESULTS: After 6 weeks of supplementation, the GS group exhibited significant increases in the serum levels of free fatty acids and glucose as well as greater maximum oxygen consumption (VO2 max, mL min-1 kg-1) compared with the placebo group in an exhaustive biking test. Following drop jump tests, the jump height and reactive strength index were increased in the GS group after completing 70 DJs. In addition, subjects in the GS group also showed decreased knee and ankle stiffness in DJs, leading to reduced fatigue associated with eccentric movement. CONCLUSIONS: GS supplementation leads to ameliorates drop jump muscle stiffness and fatigue in females and is to be used as a nutrient supplement to reduce the risk of musculoskeletal system injuries when performing drop jumps.

Accumulated Clinical Experiences from Successful Treatment of 1377 Severe and Critically Ill COVID-19 Cases.

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.

Preparation of aluminum sludge composite gel spheres and adsorption of U(IV) from aqueous solution.

A novel three-dimensional aluminum sludge/polyvinyl alcohol/sodium alginate(AS/PA/SA) gel spheres were designed and prepared for uranium(VI) adsorption, and it overcomes the shortcomings of poor recycling of powdery aluminum sludge adsorbent and poor stability of sodium alginate. Experiments show that the P-S-AS has a good pH range for removal of uranium (4-5). Fitting experimental data with pseudo-first-order kinetic model and pseudo-second-order kinetic model shows that the adsorption of U(VI) by P-S-AS is a chemical action. The fit of the Langmuir isotherm model and Freundlich isotherm model to the experimental data found that the P-S-AS adsorbed U(VI) to a single layer. Thermodynamic analysis shows that the adsorption occurs spontaneously, and an increase in temperature is favorable for the adsorption of uranium by the P-S-AS. Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis of the P-S-AS before and after adsorption showed that the main adsorption mechanism was the complexation reaction between functional groups and U(VI), the bonding reaction between metal oxides and U(VI).

[Screening and identification of GABA-producing microbes in fermentation process of Sojae Semen Praeparatum].

A high-content GABA was found in Sojae Semen Praeparatum(SSP), which is a famous traditional Chinese medicine and officially listed in Chinese Pharmacopoeia. To screen out and identify GABA-producing microbes from samples at different time points during the fermenting process of SSP, traditional microbiological methods combined with molecular biological methods were used to study the predominant GABA-producing microorganisms existing in the fermenting process of SSP. This study would lay a foundation for further studying the processing mechanism of SSP. The fermenting process of SSP was based on Chinese Pharmacopoeia(2010 edition), and samples were taken at different time points during the fermenting process of SSP. The bacteria and fungi from samples at different time points in the fermenting process of SSP were cultured, isolated and purified by selective medium, and dominant strains were selected. The dominant bacteria were cultured in the designated liquid medium to prepare the fermentation broths, and GABA in the fermentation broth was qualitatively screened out by thin-layer chromatography. The microbial fermentation broth with GABA spots in the primary screening was quantitatively detected by online pre-column derivatization and high performance liquid chromatography established in our laboratory. GABA-producing microorganisms were screened out from predominant strains, and their GABA contents in fermentation broth were determined. The DNA sequences of GABA-producing bacteria and fungi were amplified using 16S rDNA and 18S rDNA sequences by PCR respectively. The amplified products were sequenced, and the sequencing results were identified through NCBI homology comparison. Molecular biological identification was made by phylogenetic tree constructed by MEGA 7.0 software. Through the homology comparison of NCBI and the construction of phylogenetic tree by MEGA 7.0 software, nine GABA-producing microorganisms were screened out and identified in this study. They were Bacillus subtilis, Enterococcus faecium, E. avium, Aspergillus tamarii, A. flavus, A. niger, Cladosporium tenuissimum, Penicillium citrinum and Phanerochaete sordida respectively. For the first time, nine GABA-producing microorganisms were screened out and identified in the samples at different time points during the fermenting process of SSP in this study. The results indicated that multiple predominant GABA-producing microorganisms exist in the fermenting process of SSP and may play an important role in the formation of GABA.

First record of Leptospira and Blastocystis infections in captive flying squirrels (Trogopterus xanthipes) from Enshi County, China.

In traditional Chinese medicine, the feces of flying squirrels have long been used to promote blood circulation and relieve bodily stasis. However, the excrement of flying squirrels may harbor zoonotic agents that could be hazardous to public health. To understand the occurrence of bacterial and parasitic infections in this species, we investigated selected zoonotic pathogens including Leptospira and Blastocystis in the urine and feces of flying squirrels in China. Urine and fecal samples from flying squirrels were collected from a family-owned flying squirrel farm located in Enshi County, Hubei Province in China. Leptospira and Blastocystis DNA was extracted from the urine and feces of flying squirrels, and used as targets for PCR amplification, using different specific primers. PCR amplification and DNA sequencing showed that 4.4% (3/69) of flying squirrels were positive for Leptospira, while 30.4% (21/69) of the animals were positive for Blastocystis. Notably, 1.4% (1/69) of flying squirrels were found to be co-infected with Leptospira and Blastocystis. Sequence analyses allowed for the detection of 3 Blastocystis subtypes (ST1, ST3 and ST13), and mixed infections of Blastocystis subtype 1 and subtype 3 were found in 4.4% (3/69) of flying squirrels. Phylogenetic analysis of the 16S ribosomal RNA gene (rrs2), the flagellin B gene (flaB), and outer membrane lipoprotein lipL32 gene (LipL32) sequences indicated that the Leptospira species detected in the study was L. interrogans. We concluded that flying squirrels from central China were infected with Leptospira and Blastocystis, suggesting that these animals can be a source of infection for their owners, and using fresh excrement from this animal as traditional medicine could be risky to human health. To the best of our knowledge, this is the first report of Leptospira and Blastocystis infection in flying squirrels from Enshi County, China. Our findings provide new data on the epidemiology of these pathogens in this region.

Ehrlichia species in pond-farmed leeches (Hirudinaria sp.) in Hubei Province, China.

Leeches are frequently used in traditional Chinese medicine. However, they are potentially hazardous to human and animal health by transmitting several pathogens. Studies of diseases transmitted by leeches are scarce. The purpose of this study was to analyze the pathogens carried in pond-farmed medicinal leech in China. Leeches were collected from 6 farms in Hubei Province in central China. DNA was extracted from the internal organ of leeches to analyze the origin of blood meal. Leech genera were confirmed through amplification of 18S rRNA and mitochondrial gene cytochrome oxidase I (COI) gene by PCR and host animal species were identified through amplification of mitochondrial cytochrome b gene. Species of Ehrlichia in the leech specimens were screened with PCR using specific primers. PCR amplification and DNA sequencing showed that 620 leeches were Hirudinaria sp. Ehrlichia DNA was detected in 39 specimens from 2 farms. We obtained a total of 65 sequences of the cytB gene from 620 leech internal organ samples including sequences of human (n = 5), rat (n = 1), domestic pig (n = 10), duck (n = 23), goose (n = 12) and buffalo (n = 14). Phylogenetic analysis of the rrs and groEL gene sequences showed that Ehrlichia detected in the study were closely related to Ehrlichia sp. in ticks from Korea and Japan. To the best of our knowledge, this is the first report on Ehrlichia DNA being detected from leeches. Our findings provided new data on Ehrlichia spp. and farmed leech species in China.

[Effect of warm acupuncture on pathological morphology and pain-induced inflammatory mediators in rats with myofascial pain trigger].

OBJECTIVE: Based on the establishment of a rat model of trigger point, this study was to intervene with warm acupuncture, and to evaluate the effect on pathological morphology and pain-induced inflammation of the rat model by microscopic pathology and microdialysis. METHODS: Sixty-four SD rats were randomly divided into group A (blank control), group B (model control) and group C (model and intervention control). Groups A and B were divided into 3 groups (A0, A1, A2 and B0, B1, B2), the group C was divided into 2 groups (C1 and C2). The MTrPs model was established in both groups B and C, warm acupuncture intervention were given to the C1 group for 7 days and the C2 group for 15 days. Rats were sacrificed in batches. MTrPs were locally sampled and stained with hematoxylin-eosin after the preparation. The pathological changes were observed under light microscopy. The iocal interleukin-1ß and prostaglandin E2 were detected by microdialysis technique. RESULTS: Microscopically, the muscle fibers of the model were arranged disorderly, broken, twisted, local fibrosis, contracture thickening and so on; macrophage and other inflammatory cell invasion in local area and a large area of adhesion occurred on the contracture nodule, the pathological state of local muscle fibers was significantly improved after warm needle intervention, local microvascular formation and maturation, local muscle fiber repair. After successful modeling, the amount of interleukin-1ß and prostaglandin E2 in group B0 was significantly higher than that in group A0 before warm needle intervention (P<0.01). After warming intervention for 7 days, there was no significant difference in the amount of interleukin-1ß and prostaglandin E2 between group C1 and group B1 (P>0.05). Group C1 and B1 were significantly higher than group A1 (P<0.01); warm needle intervention for 15 days, the amount of interleukin-1ß and prostaglandin E2 in group C2 were lower than those in group B2 (P<0.05), but those in group C2 and B2 were significantly higher than group A2 (P<0.01), and the amount of interleukin-1ß and prostaglandin E2 in group C2 was lower than group C1 (P<0.05). CONCLUSIONS: The modeling method of exercise combined hitting used in this study was proved to be effective by histopathology; warm acupuncture can improve the pathological and inflammatory state of local muscle fiber in myofascial pain trigger of rat, promote local microvascular formation and maturation, and help the trigger point local muscle fiber repair.

Dauricine combined with clindamycin inhibits severe pneumonia co-infected by influenza virus H5N1 and Streptococcus pneumoniae in vitro and in vivo through NF-κB signaling pathway.

Dauricine, isolated from Menispermum dauricum, has been widely used for treatment of various diseases, including cardiac ischemia and inflammation-related diseases. However, little is known regarding to the effect of dauricine on severe pneumonia. Therefore, the aim was to investigate the effect of dauricine on severe pneumonia and its mechanism during progress. Herein, H5N1 and Streptococcus pneumoniae (D39) were conducted to induce severe pneumonia in both BEAS-2B cells and mice. In vitro, dauricine reversed the protein and mRNA expressions of TNF-α, IL-6 and IL-1ß, examined by ELISA and qRT-PCR assay, respectively. In addition, the nuclear translocation of NF-κB/p65 and the phosphorylation expressions of IκBα and IKKα/ß, examined by western blotting, were dose-dependently dropped by dauricine. However, dauricine had no significant effect on MAPKs, including JNK, ERK and p38. In vivo, dauricine significantly decreased MPO activity, the lung wet/dry weight ratio, the protein and mRNA expression of TNF-α, IL-6 and IL-1ß, the expressions of NF-κB/p65, and attenuated the lung histological alterations. Besides, compared to dauricine alone, combined with clindamycin had more remarkably effects on severe pneumonia in vitro. Overall, the results suggested that dauricine, a relatively drug that targets NF-κB, in combination with clindamycin, maybe a novel therapeutic strategy for severe pneumonia.

Virtual target screening reveals rosmarinic acid and salvianolic acid A inhibiting metallo- and serine-ß-lactamases.

Rosmarinic acid (RA), a polyphenolic phytochemical, has broad-spectrum biological and pharmacological activity. A virtual target screening method termed IFPTarget combined with enzyme inhibition assays led to the identification of the clinically relevant metallo-ß-lactamase (MBL) VIM-2 as one of unexploited targets of RA. The enzyme kinetic studies indicated that RA is a fully reversible, substrate-competitive VIM-2 inhibitor. The isothermal titration calorimetry (ITC) analyses revealed that the initial binding of RA to VIM-2 is mainly due to enthalpy contribution. Further inhibition assays with RA related compounds revealed that salvianolic acid A, a derivative of RA, manifests potent inhibition to VIM-2, more interestingly, which shows inhibitory activity against the NDM-1, another clinically relevant MBL subtype, and the serine-ß-lactamase TEM-1 that is structurally and mechanistically distinct from the VIM-2 and NDM-1.

Clinical Efficacy and Safety of Bathing with Chinese Medicine Taohong Siwu Decoction () for Treatment of Diffuse Cutaneous Systemic Sclerosis: A Randomized Placebo-Controlled Trial.

OBJECTIVE: To examine the efficacy and safety of bathing therapy with Taohong Siwu Decoction (, TSD) in the treatment of early-stage, mild-moderate diffuse cutaneous systemic sclerosis (dcSSc). METHODS: This randomized, placebo-controlled trial enrolled 148 men and women (18-60 years) with dcSSc (disease duration 12 months) and baseline modified Rodnan skin score (MRSS) 10. Patients were randomized into a TSD group (71 cases bathing with TSD plus oral prednisone) or control group (71 cases bathing with placebo plus oral prednisone). Bathing (40 °C, 30 min) of the upper and lower limbs was carried out once daily for 12 consecutive weeks. The primary outcome measure was MRSS; secondary outcomes were Raynaud's phenomenon (RP) score, quality of life (QOL), physician visual analogue scale (VAS), patient VAS, percent predicted diffusing capacity for carbon monoxide (DLCO), percent predicted forced vital capacity (FVC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level and overall treatment effect. RESULTS: The final analysis included 135 patients (control group, 68 cases; TSD group, 67 cases). Primary and secondary outcome measures after 2 weeks of treatment showed no improvement (versus baseline) in both groups, with no differences between groups. At 12 weeks, QOL, physician VAS, patient VAS, ESR and CRP were improved in both groups, but MRSS and RP score were improved only in the TSD group (all P<0.05). MRSS, RP score, QOL, physician VAS, patient VAS, ESR and CRP differed significantly between groups (all P<0.05). Meanwhile, the overall treatment effect was significantly higher in the TSD group than in the control group (P<0.05). Adverse events in the two groups were similar (P>0.05). CONCLUSIONS: Bathing with TSD plus oral prednisone achieves better outcomes than oral prednisone alone in patients with dcSSc and is not associated with serious adverse events.

Clinical efficacy, onset time and safety of bright light therapy in acute bipolar depression as an adjunctive therapy: A randomized controlled trial.

BACKGROUND: Bright light therapy (BLT) is an effective treatment for seasonal affective disorder and non- seasonal depression. The efficacy of BLT in treating patients with bipolar disorder is still unknown. AIMS: The aim of this study is to examine the efficacy, onset time and clinical safety of BLT in treating patients with acute bipolar depression as an adjunctive therapy (trial registration at ClinicalTrials.gov: NCT02009371). METHODS: This was a multi-center, single blind, randomized clinical trial. Seventy-four participants were randomized in one of two treatment conditions: BLT and control (dim red light therapy, dRLT). Sixty-three participants completed the study (33 BLT, 30 dRLT). Light therapy lasted for two weeks, one hour every morning. All participants were required to complete several scales assessments at baseline, and at the end of weeks 1 and 2. The primary outcome measures were the clinical efficacy of BLT which was assessed by the reduction rate of HAMD-17 scores, and the onset time of BLT which was assessed by the reduction rate of QIDS-SR16 scores. The secondary outcome measures were rates of switch into hypomania or mania and adverse events. RESULTS: 1) Clinical efficacy: BLT showed a greater ameliorative effect on bipolar depression than the control, with response rates of 78.19% vs. 43.33% respectively (p < 0.01). 2) Onset day: Median onset day was 4.33 days in BLT group. 3) BLT-emergent hypomania: No participants experienced symptoms of hypomania. 4) Side effects: No serious adverse events were reported. CONCLUSION: BLT can be considered as an effective and safe adjunctive treatment for patients with acute bipolar depression.

Therapeutic effects of curcumin nanoemulsions on prostate cancer.

The therapeutic potential of curcumin (Cur) is hampered by its poor aqueous solubility and low bioavailability. The aim of this study was to determine whether Cur nanoemulsions enhance the efficacy of Cur against prostate cancer cells and increase the oral absorption of Cur. Cur nanoemulsions were developed using the self-microemulsifying method and characterized by their morphology, droplet size and zeta potential. The results showed that the cytotoxicity and cell uptake were considerably increased with Cur nanoemulsions compared to free Cur. Cur nanoemulsions exhibited a significantly prolonged biological activity and demonstrated better therapeutic efficacy than free Cur, as assessed by apoptosis and cell cycle studies. In situ single-pass perfusion studies demonstrated higher effective permeability coefficient and absorption rate constant for Cur nanoemulsions than for free Cur. Our study suggested that Cur nanoemulsions can be used as an effective drug delivery system to enhance the anticancer effect and oral bioavailability of Cur.

Biochemical mechanism underlying hypertriglyceridemia and hepatic steatosis/hepatomegaly induced by acute schisandrin B treatment in mice.

BACKGROUND: It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly. METHODS: Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment. RESULTS: Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 103 µm2) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice. CONCLUSION: Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue.