Construction of tea tree oil/salicylic acid/palygorskite hybrids for advanced antibacterial and anti-inflammatory performance.

This study describes the construction of a tailor-made clay-based hybrid with advanced dermocompatibility, antibacterial and anti-inflammatory performance by incorporating tunable ratios of tea tree oil (TTO) and salicylic acid (SA) into the naturally occurring porous structure of palygorskite (Pal). Among the three TTO/SA/Pal (TSP) systems constructed, TSP-1 with a TTO : SA ratio of 1 : 3 demonstrated the lowest 3T3 NRU predicted acute oral toxicity and dermal HaCaT cytotoxicity as well as the most pronounced antibacterial activity with a selective inhibitory action against the pathogens (E. coli, P. acnes and S. aureus) over the beneficial (S. epdermidis) species inhabiting on the human skin. Also noticeable is that exposure of these skin commensal bacteria to TSP-1 prevented the antimicrobial resistance evolution compared to the conventional antibiotic ciprofloxacin. Mechanistic investigation of its antibacterial modes of action revealed a synergy between the TTO and SA loadings on the Pal supports in reactive oxygen production, causing oxidative damage to bacterial cell membranes and increased leakage of intracellular compounds. Additionally, TSP-1 significantly decreased the proinflammatory cytokines of IL-1ß, IL-6, IL-8, and TNF-α in a bacterial lipopolysaccharide-stimulated differentiated THP-1 macrophage model, showing the potential to inhibit inflammatory responses in bacterial infections. Overall, this is the first report exploring the potential of constructing clay-based organic-inorganic hybrids as alternatives to antibiotics to combat bacterial resistance with advanced compatibility and anti-inflammatory benefits that are desired for the development of topically applied biopharmaceuticals.

Fibrous Clays in Dermopharmaceutical and Cosmetic Applications: Traditional and Emerging Perspectives.

Functionalization of natural clay minerals for high value-added pharmaceutical and cosmetic applications receives significant research attention worldwide attributable to a rising demand and ongoing search for green, efficient, economically sustainable and ecofriendly geomaterials. Fibrous clays, i.e. palygorskite and sepiolite, are naturally-occurring hydrated magnesium aluminum silicate clay minerals with 2:1 layer-chain microstructure and one-dimensional nanofibrous morphology. Due to their unique structural, textural and compatibility features, over the past decade, fibrous clays and their organic modified derivatives are increasingly used in the dermopharmaceutical and cosmetic fields as excipients, active agents or nanocarriers to develop novel skin delivery systems or to modify drug release profile for enhanced health effects. This comprehensive review presents the up-to-date information on fibrous clays used in topically-applied products for therapeutic and cosmetic purposes with the focus on their performance-related structural characteristics and the underlying mechanisms. The recent advancement of fibrous clay-based skin delivery systems was summarized in wide range of applications including pelotherapy, wound healing, antimicrobial action, coloration and UV protection. An overview of the commonly used topically-applied dosage forms (powders, hydrogels, films, peloids and Pickering emulsion) as well as the toxicological aspects was also included, which might provide guidance to the design and development of fibrous clay-based skin delivery systems.

A Novel Hybrid Brain-Computer Interface Combining Motor Imagery and Intermodulation Steady-State Visual Evoked Potential.

The hybrid brain-computer interface (hBCI) combining motor imagery (MI) and steady-state visual evoked potential (SSVEP) has been proven to have better performance than a pure MI- or SSVEP-based brain-computer interface (BCI). In most studies on hBCIs, subjects have been required to focus their attention on flickering light-emitting diodes (LEDs) or blocks while imagining body movements. However, these two classical tasks performed concurrently have a poor correlation. Therefore, it is necessary to reduce the task complexity of such a system and improve its user-friendliness. Aiming to achieve this goal, this study proposes a novel hybrid BCI that combines MI and intermodulation SSVEPs. In the proposed system, images of both hands flicker at the same frequency (i.e., 30 Hz) but at different grasp frequencies (i.e., 1 Hz for the left hand, and 1.5 Hz for the right hand), resulting in different intermodulation frequencies for encoding targets. Additionally, movement observation for subjects can help to perform the MI task better. In this study, two types of brain signals are classified independently and then fused by a scoring mechanism based on the probability distribution of relevant parameters. The online verification results showed that the average accuracies of 12 healthy subjects and 11 stroke patients were 92.40 ± 7.45% and 73.07 ± 9.07%, respectively. The average accuracies of 10 healthy subjects in the MI, SSVEP, and hybrid tasks were 84.00 ± 12.81%, 80.75 ± 8.08%, and 89.00 ± 9.94%, respectively. The high recognition accuracy verifies the feasibility and robustness of the proposed system. This study provides a novel and natural paradigm for a hybrid BCI based on MI and SSVEP.

[Narrative evidence-based medicine:a strategy for evaluation of clinical efficacy of Chinese medicine].

Rich experience of clinical diagnosis and treatment has been accumulated in the developmental history of Chinese medicine, and the efficacy has been increasingly accepted by the public. However, the evaluation of clinical efficacy is currently based more on scientific evidence instead of merely the changes of patient symptoms. In Chinese medicine, the changes of major disease indicators, patient symptoms, and pathogenesis are the major criteria for the evaluation of clinical efficacy. The lack of well-accepted and uniform criteria and the uncertainty of subjective evaluation limit the development of clinical Chinese medicine. Evidence-based medicine combines clinical skills with the current best evidence. Narrative medicine, utilizing people's narratives in clinical practice, emphasizes patient feelings, willingness, and value orientation. The introduction of both evidence-based medicine and narrative medicine into the evaluation of clinical efficacy refers to the construction of the clinical efficacy evaluation system in a paradigm of participatory diagnosis and treatment. It can fully reflect the characteristics of Chinese medicine, respect the values of patients, and achieve universal clinical evidence. Therefore, it helps to improve the diagnosis and treatment, the relationship between doctors and patients, patients' life quality and decision-making awareness, and finally the new evaluation model of clinical efficacy of Chinese medicine.

Computational Medicine: Past, Present and Future.

Computational medicine is an emerging discipline that uses computer models and complex software to simulate the development and treatment of diseases. Advances in computer hardware and software technology, especially the development of algorithms and graphics processing units (GPUs), have led to the broader application of computers in the medical field. Computer vision based on mathematical biological modelling will revolutionize clinical research and diagnosis, and promote the innovative development of Chinese medicine, some biological models have begun to play a practical role in various types of research. This paper introduces the concepts and characteristics of computational medicine and then reviews the developmental history of the field, including Digital Human in Chinese medicine. Additionally, this study introduces research progress in computational medicine around the world, lists some specific clinical applications of computational medicine, discusses the key problems and limitations of the research and the development and application of computational medicine, and ultimately looks forward to the developmental prospects, especially in the field of computational Chinese medicine.

Simultaneous determination of eleven major components in Fugan Fang using high-performance liquid chromatography coupled with mass spectrometry.

Fugan fang (FGF) is a traditional Chinese medicine (TCM) prescription that has been used in treating hepatic illnesses for many years. In this study, an analytical method is developed for the quantitative analysis of the major components of FGF. This method is based on high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) on a reverse-phase C18 column. Results show that 0.01% acetic acid and acetonitrile is the optimum mobile phase in gradient elution. All compounds showed good linearity (r(2) ≥ 0.9948). Recoveries measured at three concentration levels varied from 83.5 to 104.8%. The method was validated with respect to precision, repeatability and accuracy and was successfully applied in the quantification of the 11 components of FGF products. The validated HPLC-MS method provides a basis for assessing the quality of TCM prescriptions containing many bioactive components.

Content determination of the major constituents of Yinchenzhufu decoction via ultra high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry.

In this study, we developed a method using ultra high-performance liquid chromatography coupled with electrospray ionisation tandem mass spectrometry for determining the contents of chlorogenic acid, atractylenolide I, atractylenolide III, benzoylaconine, benzoylmesaconine, benzoylhypaconine, glycyrrhizic acid, glycyrrhetic acid, liquiritigenin, and cinnamic acid in Yinchenzhufu decoction, a classic traditional Chinese medicine prescription. Separation was performed on a C18 column (4.6mm i.d.×250mm, 5µm) and achieved with good linearity (r(2)>0.9984) within 35min. Gradient elution was applied using a mobile phase of 0.05% acetic acid/acetonitrile. The analytes were quantified on an LCQ ion trap mass spectrometer in electrospray ionisation full-scan mode. Variations in the intra- and inter-day precision of all analytes were below 4.57%, and the accuracy was evaluated by a recovery test within the range of 97.88-102.25%. The method successfully quantified the 10 compounds in five sample batches of Yinchenzhufu decoction, and the results show that the method is accurate, sensitive, and reliable.

[Chinese herbal medicine Fuzheng Huayu recipe inhibits liver fibrosis by mediating the transforming growth factor-ß1/Smads signaling pathway].

OBJECTIVE: To investigate the mechanism of Fuzheng Huayu recipe (FZHY), a compound traditional Chinese herbal medicine, against liver fibrosis related to transforming growth factor-ß1 (TGF-ß1)/Smads signaling transduction. METHODS: The research consisted of in vitro and in vivo experiments. In the in vivo experiment, 37 male Wistar rats were divided into 3 groups: 5 rats in normal group, 18 and 14 rats respectively in model and FZHY groups. Liver fibrosis was induced in rats of the model group and the FZHY group by intraperitoneal injection of dimethylnitrosamine with a dose of 10µg/kg body weight for 4 weeks. Rats in the FZHY group were administered with FZHY for 4 weeks after liver fibrosis was induced. After the treatment of FZHY, hydroxyproline (Hyp) content in rat liver tissue was assayed by Jamall's method and protein expressions of TGF-ß1, TGF-ß1 receptor I (TßR-I), Smad2, Smad3 and phosphorylated-Smad2/3 were analyzed by Western blotting. In the in vitro experiment, hepatic stellate cells (HSCs) were isolated from normal rats by in situ pronase/collagenase perfusion followed by density gradient centrifugation. On the 4th day of cell culture, HSCs were stimulated by 2.5 ng/mL TGF-ß1 for 24 h, then incubated with the medium containing 10% FZHY-medicated serum or 10µmol/L SB-431542 (a potent and specific inhibitor of TGF-ß1 receptor I kinase) for 24 h. And the HSCs without TGF-ß1 stimulating were used as control group. Protein expressions and location of α-smooth muscle actin (α-SMA) and Smad3 in HSCs were assayed by immunofluorescent staining, and the image was analyzed by Image-Pro Plus 6.1 System. RESULTS: In the in vivo experiment, liver Hyp content in the FZHY group was reduced significantly compared with the model group. FZHY also down-regulated the protein expressions of TGF-ß1, TßR-I and p-Smad2/3 in fibrotic liver tissue. In the in vitro experiment, FZHY-medicated serum incubated with TGF-ß1-stimulated HSCs significantly down-regulated the protein expression of α-SMA. It also inhibited Smad3 nuclear translocation in TGF-ß1-stimulated HSCs. CONCLUSION: The mechanism of FZHY against liver fibrosis is related to the regulation of TGF-ß1 signaling transduction pathway by inhibition of TGF-ß1 and TßR-I expressions and Smads activation in fibrotic liver tissue and HSCs.

[Effects of salviandic acid B (SA-B) on activity of basement membrane-type collagenase and impact of regulatory factors in rats with cardiac hypertrophy].

OBJECTIVE: To observe the effect of salviandic acid B (SA-B) on MMP-2/9 and TIMP-2 of fibrotic cardiac tissues in rats and explore the action mechanism of SA-B anti-fibrosis of heart. METHOD: Ventricular remodeling model was induced by abdominal aortic banding (AAB) in rats. Rats were randomly divided into 6 groups: normal, model, SA-B high, SA-B middle, SA-B low and captopril control group. Histological changes of heart were observed with hemotoxylin and eosin (H&E) staining and Sirius red staining. Hydroxyproline (Hyp) content in heart tissue was measured by hydrolysis method. Expression of heart tissue collagen NIV, MMP-2/9 and TIMP-2 were analyzed with Western blot The activities of heart tissue MMP-2 were determined with gelatin zymography substrate degradation method. RESULT: SA-B treated groups had lower heart inflammation and lower heart Hyp content; decreased Collagen deposit and alleviated cardiac fibrosis. SA-B treated groups obviously decreased the expression of Collagen IV, MMP-2/9 and TIMP-2. The activity of MMP-2 was decreased in treated SA-B treated groups. CONCLUSION: The mechanism of SA-B action against cardiac fibrosis may be related to down-regulating the expression of TIMP -2 and the activity of MMP-2/9, thus protect the normal basal membrane.

Somatosensory evoked potential compotents with and without contact cold stimulus.

In the present study, somatosensory evoked potentials following contact cold painful stimulation of the posterior tibial nerve (PTN) at left and right ankle were investigated in 4 normal subjects. By fitting dipole models to independent components, more sources were found in pain status than in non pain condition. Among these fitted components, three SEPs related components and one pain related component were observed. Corresponding to the specific components, generating sources of SEPs were located at primary somatosensory cortices, anterior cingulate and thalamus, supporting the previous findings, while the pain specific generator was found at primary somatosensory cortices or primary motor cortices. However, former reports have shown more sources than those found in this study, which may be caused by overlaping of conventional SEPs and pain sources. Consequently, the connectivity of these sources will be studied to better understandthe information flow and function of these components and sources.

All-trans retinoic acid enhances murine dendritic cell migration to draining lymph nodes via the balance of matrix metalloproteinases and their inhibitors.

Cancers escape immune surveillance through the manipulation of the host's immune system. Sequestration of dendritic cells (DCs) within tumor tissues and the subsequent inhibition of their migration is one of the several mechanisms by which tumors induce immunosuppression. In view of recent findings depicting the improvement of tumor immune responses in cancer patients following all-trans retinoic acid (ATRA) treatment, we sought to identify the effects of ATRA on DC mobility in the context of tumor immunotherapy. Our results demonstrate that ATRA, added to differentiating murine bone marrow progenitor cells, enhances the invasive capacity of the resulting DCs. Immature DCs injected intratumorally in mice show increased accumulation in draining lymph nodes, but not in nondraining lymph nodes and spleens, when differentiated in the presence of ATRA. The in vitro migration of mature DCs through the basement membrane matrix toward the lymphoid chemokines CCL19 and CCL21 is enhanced in these cells, albeit not in the presence of a matrix metalloproteinase (MMP) inhibitor. An increase in MMP production with a simultaneous decrease in the production of their inhibitors (tissue inhibitors of matrix metalloproteinase or TIMPs) is provoked by ATRA. This affects the MMP/TIMP balance in DCs, in particular that of MMP-9 and TIMP-1, favoring protease activity and thus allowing for enhanced DC mobilization. In conclusion, this study demonstrates that ATRA is capable of improving DC trafficking in a tumor milieu and, in view of the encouraging results obtained in the clinic, further supports the notion that ATRA might be a valuable chemical adjuvant to current immunotherapeutic strategies for cancer.

[Effects of Fuzheng Huayu recipe on renal toxic interstitial fibrosis in rats].

OBJECTIVE: To investigate the effects of Fuzheng Huayu Recipe on renal interstitial fibrosis in rats induced by the toxic substances. METHODS: Forty Wistar rats were divided into 3 groups, including the normal group, model control and Fuzheng Huayu Recipe treated group. The renal fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN) for 4 weeks and oral administration of food containing heavy metals such as Hg, etc for 8 weeks. From the 5th week, the rats were orally administered Fuzheng Huayu Recipe for 4 weeks. The renal tissue was stained with HE and periodic acid-silver metheramine, respectively. The serum creatinine and urea nitrogen were assayed with the kits, and the renal hydroxyproline (Hyp) contents in the homogenate of kidney tissue were measured with HCl hydrolysis. RESULTS: In the model group, the renal tubule was swollen, and the tubular epithelial cells were degenerated, necrosed and detached, with the infiltration of inflammatory cells; the tubular interstitium was expanded, characterized with the deposition of large collagens; the tubular basement membrane became thicker and wrinkled; and the renal Hyp content and serum creatinine and urea nitrogen levels increased remarkably as compared to the normal group. After the treatment with Fuzheng Huayu Recipe, the renal tubular inflammation and interstitial collagen deposition were alleviated, and the serum creatinine and urea nitrogen levels decreased significantly as compared to the model group. CONCLUSION: Administration of DMN and heavy metals can induce the renal interstitial fibrosis and impair the renal function. Fuzheng Huayu Recipe can improve the impaired renal functions and reverse the renal interstitial fibrosis.