Two-Dimensional Biodegradable Black Phosphorus Nanosheets Promote Large Full-Thickness Wound Healing through In Situ Regeneration Therapy.

Large full-thickness skin lesions have been one of the most challenging clinical problems in plastic surgery repair and reconstruction. To achieve in situ skin regeneration and perfect clinical outcomes, we must address two significant obstacles: angiogenesis deficiency and inflammatory dysfunction. Recently, black phosphorus has shown great promise in wound healing. However, few studies have explored the bio-effects of BP to promote in situ skin regeneration based on its nanoproperties. Here, to investigate whether black phosphorus nanosheets have positive bio-effects on in situ skin repair, we verified black phosphorus nanosheets' positive effects on angiogenic and anti-inflammatory abilities in vitro. Next, the in vivo evaluation performed on the rat large full-thickness excisional wound splinting model more comprehensively showed that the positive bio-effects of black phosphorus nanosheets are multilevel in wound healing, which can effectively enhance anti-inflammatory ability, angiogenesis, collagen deposition, and skin re-epithelialization. Then, multiomics analysis was performed to explore further the mechanism of black phosphorus nanosheets' regulation of endothelial cells in depth. Molecular mechanistically, black phosphorus nanosheets activated the JAK-STAT-OAS signaling pathway to promote cellular function and mitochondrial energy metabolism in endothelial cells. This study can provide a theoretical basis for applying two-dimensional black phosphorus nanosheets as nanomedicine to achieve in situ tissue regeneration in complex human pathological microenvironments, guiding the subsequent optimization of black phosphorus.

Fabrication of a curcumin encapsulated bioengineered nano-cocktail formulation for stimuli-responsive targeted therapeutic delivery to enhance anti-inflammatory, anti-oxidant, and anti-bacterial properties in sepsis management.

This study aimed to fabricate an eco-friendly functionalized chitosan (CS) nanocarrier to establish a pH-responsive drug delivery system for the treatment of sepsis. Curcumin (Cur) and cerium oxide (CeO2) were loaded onto an octenylsuccinic anhydride (OSA)-functionalized CS nanoformulation (Cur@Ce/OCS) to achieve an effective nanocarrier (NC) for sepsis treatment. The physicochemical characteristics of the developed nanocarriers were determined using various characterization techniques. The developed CeO2-OCS nanoformulation has been showed effective anti-bacterial activity (∼97%) against G+ and G- bacterial pathogens, and also have improved drug loading (94% ± 2), and encapsulation efficiency (89.8% ± 1.5), with uniform spherical particles having an average diameter of between 100 and 150 nm. The in vivo experimental results establish that Cur-loaded Ce/OCS NPs could have enhanced therapeutic potential against lung infection model by reducing bacterial burden and extensively decreasing inflammatory responses in sepsis model. Additionally, we determined the in vivo biosafety of the nanoformulations by histological observation of different mouse organs (heart, liver, spleen, and kidney), and observed no signs of toxicity in the treatment groups. The findings of this study clearly demonstrate the therapeutic potential of pH-sensitive nanoplatforms in the management of infectious sepsis.

Cyasterone inhibits IL-1ß-mediated apoptosis and inflammation via the NF-κB and MAPK signaling pathways in rat chondrocytes and ameliorates osteoarthritisin vivo.

Osteoarthritis is a prevalent global joint disease, which is characterized by inflammatory reaction and cartilage degradation. Cyasterone, a sterone derived from the roots of Cyathula officinalis Kuan, exerts protective effect against several inflammation-related diseases. However, its effect on osteoarthritis remains unclear. The current study was designed to investigate the potential anti-osteoarthritis activity of cyasterone. Primary chondrocytes isolated from rats induced by interleukin (IL)-1ß and a rat model stimulated by monosodium iodoacetate (MIA) were used for in vitro and in vivo experiments, respectively. The results of in vitro experiments showed that cyasterone apparently counteracted chondrocyte apoptosis, increased the expression of collagen II and aggrecan, and restrained the production of the inflammatory factors inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), metalloproteinase-3 (MMP-3), and metalloproteinase-13 (MMP-13) induced by IL-1ß in chondrocytes. Furthermore, cyasterone ameliorated the inflammation and degenerative progression of osteoarthritis potentially by regulating the nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. For in vivo experiments, cyasterone significantly alleviated the inflammatory response and cartilage destruction of rats induced by monosodium iodoacetate, where dexamethasone was used as the positive control. Overall, this study laid a theoretical foundation for developing cyasterone as an effective agent for the alleviation of osteoarthritis.

Streptomyces: Derived Active Extract Inhibits Candida albicans Biofilm Formation.

Candida albicans is an opportunistic pathogen that causes biofilm-associated infections. C. albicans biofilms are known to display reduced susceptibility to antimicrobials and high rates of acquired antibiotic resistance, and biofilm forming in C. albicans further hampers treatment options and highlights the need for new antibiofilm strategies. Identifying active components from desert actinomycetes strains to inhibit the formation of C. albicans biofilms represents an effective treatment strategy. In this study, actinomycetes that can inhibit C. albicans biofilm formation were isolated from the Taklimakan Desert, and the underlying mechanisms were explored. After screening the anti-C.albicans biofilm activities of culture supernatants from 170 Actinomycete strains, six strains showed significant inhibition of C. albicans biofilm formation. Microscopic examination showed a reduction in biofilm formation of C. albicans treated with supernatants from actinomycetes. Scanning electron microscopy showed that the morphological changes in biofilm cells were caused by cell membrane rupture and cell material leakage. Then, C.albicans biofilms were destroyed by changing the content of extracellular polysaccharides or degrading extracellular DNA. Finally, a preliminary study on active substances extracted from a new species (TRM43335) showed that the substances that inhibited the formation of biofilms might be peptides. This study provides preliminary evidence that desert actinomyces strains have inhibitory effects on the biofilm development of C. albicans.

Three New Xanthones from Hypericum scabrum and Their Quorum Sensing Inhibitory Activities against Chromobacterium violaceum.

Quorum sensing (QS) plays an important role in the production of virulence factors and pathogenicity in pathogenic bacteria and is, therefore, a hopeful target to fight against bacterial infections. During our search for natural QS inhibitors, two new xanthonolignoids (1 and 2), each existing as a racemic mixture, one new simple oxygenated xanthone (7), and eight known analogs (3-6, 8-11) were isolated from Hypericum scabrum Linn. Chiral separation of 1 yielded a pair of enantiomers 1a and 1b. The structures of these compounds were elucidated by spectroscopic analysis and ECD (electrostatic circular dichroism) calculations. All isolates were evaluated for their QS inhibitory activity against Chromobacterium violaceum. Both 9 and 10 exhibited the most potent QS inhibitory effects with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 31.25 and 62.5 µM, respectively. Crystal violet staining was used to further evaluate the biofilm inhibition potential of compounds 7, 9 and 10, and the formation of biofilms increased with decreasing drug concentration in a classic dose-dependent manner. The results of a cytotoxicity assay revealed that compounds 7, 9 and 10 exhibited no cytotoxic activity on PC-12 cells at the tested concentration.

Anti-proliferation and anti-inflammation effects of corilagin in rheumatoid arthritis by downregulating NF-κB and MAPK signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried aboveground part of Geranium Wilfordii Maxim. (G. Wilfordii) is a traditional Chinese herbal medicine named lao-guan-cao. It has long been used for dispelling wind-dampness, unblocking meridians, and stopping diarrhea and dysentery. Previous investigations have revealed that 50% ethanolic extract of G. Wilfordii has anti-inflammatory and anti-proliferation activities on TNF-α induced murine fibrosarcoma L929 cells. Corilagin (COR) is a main compound in G. Wilfordii with the content up to 1.69 mg/g. Pharmacology study showed that COR has anti-inflammatory, anti-tumor, anti-microorganism, anti-oxidant, and hepatoprotective effects. However, there is no any investigation on its anti-proliferation and anti-inflammation effects in rheumatoid arthritis (RA). AIM OF THE STUDY: The present study aimed to evaluate the potential pharmacological mechanisms of anti-proliferation and anti-inflammation effects of COR in RA. MATERIALS AND METHODS: In vitro, MH7A cells model induced by IL-1ß was used. The anti-proliferation activity of COR was assessed by Cell Counting Kit-8 (CCK-8) assay, and the anti-migration and anti-invasion activity of COR was determined by wound healing assay and transwell assay, respectively. Furthermore, apoptosis assay by flow cytometer was used to measure the pro-apoptotic effect of COR. The mRNA expressions of Bax, Bcl-2, IL-6, IL-8, MMP-1, MMP-2, MMP-3, MMP-9, COX-2, and iNOS were measured by qRT-PCR, and related protein were further verified by ELISA kits or Western blot. Moreover, protein levels associated with NF-κB and MAPK signaling pathways of p65, P-p65, IκBα, P-IκBα, ERK1/2, P-ERK1/2, JNK, P-JNK1/2/3, p38, and P-p38 were determined by Western blot. The nuclear translocation of NF-κB-p65 was detected by immunofluorescent staining. In vivo, adjuvant-induced arthritis (AIA) rat model was used, and the body weight, paw swelling, and arthritis score during the entire period were measured. Histopathological analysis of joints of synovial tissues was also determined. The expression of pro-inflammatory cytokines in serum including IL-6, TNF-α, IL-1ß, and IL-17 were measured. RESULTS: The in vitro results showed that COR could dose-dependently inhibit the proliferation, migration, and invasion of IL-1ß-induced MH7A cells, as well as promote its apoptosis. Moreover, it also suppressed the over-expression of Bcl-2, IL-6, IL-8, MMP-1, MMP-2, MMP-3, MMP-9, COX-2, and iNOS while up-regulated the level of Bax. Besides, the ratios of P-p65/p65, P-IκBα/IκBα, P-ERK/ERK, P-JNK/JNK, and P-p38/p38 were decreased, and the nuclear translocation of p65 induced by IL-1ß was blocked by COR. In vivo results indicated that COR significantly reduced the paw swelling and arthritis score in AIA rats, and inhibited synovial tissue hyperplasia and erosion, as well as inflammatory cells infiltration. It also decreased the serum pro-inflammatory cytokines (IL-6, TNF-α, IL-1ß, and IL-17) production. CONCLUSION: These results revealed that COR exerted anti-rheumatoid arthritis effect, and its underlying mechanisms may be related to inhibiting the proliferation, migration, and invasion of synovial fibroblasts, enhancing cell apoptosis, and suppressing inflammatory responses via downregulating NF-κB and MAPK signaling pathways.

Fracture risks in patients with atopic dermatitis: A nationwide matched cohort study.

BACKGROUND: The risk of osteoporosis has been explored in atopic dermatitis (AD). The long-term risk of fractures in patients with AD and the effects of various AD treatments on bone health remain to be elucidated. OBJECTIVE: To evaluate the long-term risk of fractures in patients with AD. METHODS: This nationwide matched cohort study was conducted using the National Health Insurance Research Database of Taiwan for the period 1997 to 2013. A total of 36,855 patients with AD and 147,420 reference subjects without AD were identified. Demographic characteristics and comorbidities were compared, and cumulative incidence of fractures was evaluated. Adjusted hazard ratios for fracture risks of AD and various AD treatments were calculated using the Cox proportional hazards model. RESULTS: A total of 1518 patients (4.12%) in the AD cohort and 5579 patients (3.78%) in the reference cohort had fractures (P = .003). The mean ages were 22.6 years in both groups. The 16-year cumulative incidence of fractures in the AD cohort (8.043%) was significantly higher than that in the reference cohort (7.366%) (P = .002). Severe AD (adjusted hazard ratio [aHR], 1.31; 95% confidence interval [CI], 1.08-1.59) was independently associated with fractures. Other independent risk factors included exposure to topical (aHR, 1.21; 95% CI, 1.05-1.39) or systemic (≥10 mg/d; aHR, 1.62; 95% CI, 1.38-1.91) corticosteroids. Use of disease-modifying antirheumatic drugs (aHR, 0.71; 95% CI, 0.53-0.90) and phototherapy (aHR, 0.73; 95% CI, 0.56-0.95) was associated with a lower risk of fractures. The results were consistent across sensitivity analyses. CONCLUSION: Patients with AD have a higher incidence of fractures. Severe AD is independently associated with fractures.

The traditional uses, phytochemistry, and pharmacology of Stemona species: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of genus Stemona (Stemonaceae) have been long used locally and traditionally in many South and East Asian counties to relieve cough, dispel phlegm, prevent asthma, control pests, diminish inflammation, decrease pain, and treat some cutaneous diseases. AIM OF STUDY: This review provided comprehensive and up-to-date information about botanic characterization and distribution, ethnopharmacology, secondary metabolites, pharmacological activities, and toxicology of plants of genus Stemona to explore the scientific potential and future therapeutic potential of the plants. MATERIALS AND METHODS: This article conducted a literature review on information about the Stemona species in multiple electronic databases, including PubMed, Web of Science, Wiley, Science Direct, Elsevier, Google Scholar, ACS publications, SpringerLink, and China National Knowledge Internet. Information was also derived from other literature sources (e.g. Chinese Pharmacopoeia, 2015 edition, Chinese herbal classic books, PhD and MSc thesis). Plant names were validated by "The Plant List" (www.theplantlist.org). All studies of the genus Stemona were included in this review until March 2020. RESULTS: Our comprehensive analysis of the scientific literatures indicated that many Stemona species are popular and valuable herbal medicines with therapeutic potentials to treat various ailments. Phytochemical analyses identified alkaloids and stilbenoids as the major bioactive substances of Stemona species. Numerous studies have shown that the extracts and secondary metabolites isolated from these plants have a wide range of pharmacological activities, including insecticidal and antifeedant, antitussive, anti-inflammatory, anticancer, antimicrobial, and antivirus activities. CONCLUSION: Though plants of genus Stemona have been put to enormous traditional uses, the pharmacological studies conducted were insufficient. Therefore, more secondary metabolites need to be studied for more detailed pharmacological studies. Further studies are also required to establish the mechanisms which mediate the plants' bioactivities in relation to the medicinal uses as well as investigate any potential toxicity for future clinical studies.

Investigation on Mechanism of Jianzhong Bushen Xiaozheng Decoction Against Renal Interstitial Fibrosis in Regulating Wnt/β-catenin Signaling Pathway by MiRNA-139 / 中国实验方剂学杂志

Objective:To investigate the mechanism of Jianzhong Bushen Xiaozheng decoction in regulating the effect of miRNA139 on Wnt/<italic>β</italic>-catenin signaling pathway for renal interstitial fibrosis. Method:The 120 mice were randomly divided into sham operation group， unilateral ureteral obstruction （UUO） group， Jianzhong Bushen Xiaozheng decoction low， middle， high dose group， and Niaoduqing group. The UUO animal model was established to observe the morphological changes in mice. Intragastic administration was started from day 3 after modeling. The sham operation group and UUO group received the same amount of distilled water every day. The low， medium and high-dose groups received Jianzhong Bushen Xiaozheng decoction solution at 6，12，24 g·kg^-1·d^-1 respectively. The Niaoduqing group received 6.2 g·kg^-1·d^-1 Niaoduqing granule solution. After 14 d and 21 d， 28 d ， the morphological changes， general signs and renal interstitial fibrosis index of the obstructed side were observed， hematoxylin-eosin （HE） staining and Masson staining were used to observe the pathological changes of renal tissue. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） method was used to detect the miRNA-139 expression in renal tissue volume， Western blot was used to detect expression of beta serial proteins （<italic>β</italic>-catenin） and fibrinolytic enzyme activators inhibitor-1 （PAI-1） in renal tissues， and immunohistochemical assay was used for detection of matrix metalloproteinases-7 （MMP-7） protein expression at the obstruction side. Result:After 14， 21 and 28 days， the expression levels of <italic>β</italic>-catenin and PAI-1 in UUO group were higher than those in sham operation group（<italic>P</italic><0.05），while the expression levels of miRNA139 and MMP-7 protein were lower than those of sham operation group （<italic>P</italic><0.05）. The expression levels of <italic>β</italic>-catenin and PAI-1 proteins in mice after treatment in Niaoduqing group and the traditional Chinese medicine groups were lower than those in the UUO group（<italic>P</italic><0.05）， the expression of miRNA139 and MMP-7 proteins increased（<italic>P</italic><0.05）， and the efficacy of high-dose Jianzhong Bushen Xiaozheng decoction group was better than that of other dosage groups or Niaoduqing group（<italic>P</italic><0.05）. Conclusion:Jianzhong Bushen Xiaozheng decoction may regulate miRNA139 to mediate the process of renal interstitial fibrosis through the Wnt/ <italic>β</italic>-catenin pathway and delay the development of renal interstitial fibrosis to improve renal function.

[The role of submerged group ecological media box in repairing black and odorous water body]. / 潜水式生态介质箱对黑臭水体的修复效果.

As a conventional technology, the ecological floating bed has been widely used to repair waste water body. However, it can only repair the surface oxygen-enriched water, and has limited ability to repair the lower anoxic water. To meet the needs of the restoration of black and odorous water body, we designed a submersible ecological media box (submerged group) and compared it with traditional ecological floating bed (floating bed group). Water quality of black and odorous water before and after the restoration was examined, with the growth status of aquatic plants and the accumulation ability of N and P being investigated. The results showed that with the prolongation of repairing time, the removal rate of each pollutant increased gradually in both treatments. The removal ability of the submerged group for TN, NH4+-N, TP was better than that of the floating bed group, but its ability to remove CODMn was slightly inferior than that of the floating bed group. Plants (Vallisneria natans) in the submerged group grew better than that in the floating bed group (Acorus cala-mus), with similar patterns of the absorption and accumulation capacity and removal rate of TN and TP. In addition, the plasma membrane permeability and malondialdehyde content of V. natans were lower than that of A. calamus and the chlorophyll content of A. calamus was higher than that of V. natans, indicating that V. natans is more suitable for planting in black and odorous water bodies. Thus, the submersible ecological media box is a new in-situ integrated remediation device, which is more suitable to repair the black and odorous water.

Pityriasis Lichenoid-like Mycosis Fungoides in a 9-year-old Boy: A Case Report.

Dear Editors, Pityriasis lichenoides (PL)-like mycosis fungoides (MF) is a rare variant of MF, presenting clinical findings of PL but histological features of MF. It was first reported by Ko et al. (1) and only a few cases have been reported since (2-5). Herein we report the case of a boy with PL-like MF and review the related literature. A 9-year-old boy presented with a 1-year history of multiple pruritic crusted erythematous papules and scaly pink maculopatches on the face, trunk, and extremities (Figure 1, a and b). Histologic examination of a papule revealed lymphocytic epidermotropism and lymphocytes tagging the dermoepidermal junction. The nuclei of the lymphocytes were hyperchromatic and irregular (Figure 1, c and d). Immunohistochemically, the infiltrating lymphocytes revealed positivity for CD2, CD3, CD5, CD7, and CD8, but were negative for CD4, CD20, CD30, CD68, and CD163 (Figure 1, e-g). T-cell receptor gene rearrangement analysis (TCR-GRA) demonstrated the rearrangement of the gamma chain (Figure 1, h). PL-like MF was diagnosed. The patient was started on narrowband ultraviolet B (NBUVB) phototherapy. The skin lesions markedly improved after 6 months of treatment. There was no recurrence during the 2 years of follow-up. There has long been a controversy regarding whether PL is just an inflammatory dermatosis or a genuine T-cell lymphoproliferative disease. Wang et al. (2) proposed three categories for the relationship between PL and MF: (A) PL with a dominant T-cell clone, (B) PL subsequently progressing into MF, and (C) PL-like MF. In the first category, PL is a monoclonal T-cell-mediated inflammatory disorder, in which T-cell clones were found in about 50% of patients (6,7). The second category involves progression from long-term PL to MF (8,9). The average time-to-progression is about 8 years. It has been speculated that the PL-related immunologic microenvironment is favorable for developing a tumoral clone. Our patient presented with PL-like lesions clinically, while biopsy findings, results of immunohistochemistry, and TCR-GRA all suggested that this case was MF. Due to the short duration (only one year) of his lesions, we established the diagnosis of PL-like MF de novo, rather than evolution from PL to MF. The features of previously reported cases of PL-like MF and those of our patient are summarized in Table 1 (1-5). Men were predominant (18:7) among the total of 25 patients. Most patients were children or young adults (mean age of 23.4 years).The interval between presence of lesions and diagnosis varied from 1 month to 10 years. The cutaneous eruptions were all PL in appearance and almost all involved both the trunk and extremities. Pruritus was reported by approximately half of the patients. Histologically, the scaly papules were usually indistinguishable from classical MF, showing epidermotropism, haloed lymphocytes, lymphocytes aligning along the dermoepidermal junction, and Pautrier's microabscesses. Immunohistochemically, all tested cases demonstrated positivity for CD3 but were negative for CD20 and CD30. Cases with predominantly CD8-positive cells were twice as prevalent as cases with predominantly CD4-positive cells. TCR-GRA was performed in 20 cases, 15 of which revealed monoclonality. Most patients received psoralen combined with ultraviolet A or NBUVB phototherapy, and demonstrated either a complete or partial response. Recurrence was reported in only 2 cases (5). In summary, PL-like MF is a rare variant of MF. It has some features distinct from classic MF, such as a higher incidence in young men and predominantly CD8-positive T-cells infiltration. Phototherapy can be used as the first line of treatment. A good response and a favorable prognosis can be expected.

Risk of skin cancer in psoriasis patients receiving long-term narrowband ultraviolet phototherapy: Results from a Taiwanese population-based cohort study.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) phototherapy is a widely used treatment for various dermatoses. The risk of skin cancer following long-term NB-UVB phototherapy has rarely been explored in skin phototypes III-V. METHODS: We conducted a nationwide-matched cohort study and identified a total of 22 891 psoriasis patients starting NB-UVB phototherapy from the Taiwan National Health Insurance Database during the period 2000-2013. Cumulative incidences of skin cancers were compared between subjects receiving less than 90 UVB treatments (S-cohort, N = 13 260) and age- as well as propensity score-matched subjects receiving more than or equal to 90 UVB treatments (L-cohort, N = 3315). RESULTS: There were no significant differences in the overall cumulative incidences of skin cancers between the two cohorts (log-rank t test, P = 0.691) during the follow-up periods. The S-cohort had a significantly lower prevalence of actinic keratosis when compared with the L-cohort (0.54% vs 1.00%, P = 0.005). CONCLUSION: Long-term NB-UVB phototherapy does not increase skin cancer risk compared with short-term NB-UVB phototherapy in psoriasis patients with skin phototypes III-V.

Niga-ichigoside F1 ameliorates high-fat diet-induced hepatic steatosis in male mice by Nrf2 activation.

Hepatic lipid accumulation and oxidative stress (OS) lead to non-alcoholic fatty liver disease (NAFLD). Thus, we hypothesized that antihyperlipidemic and antioxidant activities of niga-ichigoside F1 (NI) would ameliorate events leading to NAFLD. Lanbuzheng (Geum japonicum Thunb. var. chinense), a type of wild vegetable found in Southwest China, was used to extract NI. Male C57BL/6J mice were fed a standard diet (Con) or a high-fat diet (HFD) (denoted as diet) with or without 40 mg kg-1 NI (defined as treatment) for 12 weeks. Diet-treatment interactions were observed in the final body weight, fat pad mass, respiratory exchange ratio (RER) in the daytime, and energy expenditure during the whole day. Moreover, NI alleviated hepatic steatosis, possibly by significantly interacting with HFD to regulate lipid metabolism genes (including Srebp1c, Acc1, Fasn, Scd1, Cpt1a and Fabp5). We also found significant diet-treatment interactions on superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) activities, and thiobarbituric acid reactive substance (TBARS) levels, as well as the nuclear and cellular Nrf2 protein levels. Significant free fatty acid (FFA)-treatment interactions on Nrf2 nuclear translocation, antioxidant enzymes activities, genes in lipogenesis (Srebp1c, Acc1, Fasn, and Scd1), and fatty acid oxidation (Pparα) and transport (Fabp5 and Cd36) were also detected in 1 mM FFA-treated HepG2 cells with or without 20 µM NI. These beneficial effects of NI on oxidative stress and lipid accumulation were abolished by Nrf2 siRNA. Our data revealed that dietary NI could prevent HFD-induced hepatic steatosis, possibly via interacting with HFD to activate Nrf2 nuclear translocation to maintain a redox status, thus regulating lipid metabolism genes expressions.

Failure patterns of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma: implications for the target area design of postoperative therapy / 中华放射医学与防护杂志

Objective To analyze the failure patterns and prognostic factors of radical surgery in patients with T1-4N0-1M0 thoracic esophageal squamous cell carcinoma (TESCC),and the implications for the target area design of postoperative therapy.Methods We retrospectively analyzed 1 191 patients with TESCC who underwent radical surgery at our institution.The failure patterns,the prognostic factors,as well as the effects of lesion locations and N stage on the failure patterns were analyzed.Results The thoracic-region recurrence rate and the distant metastasis rate was 31.7％ and 16.4％ in all patients.The multivariate analysis showed that the lesion locations,the degree of inflammatory adhesion,T staging,N staging and the rate of lymph nodes metastasis were independent factors affecting the regional recurrence (P ＜ 0.05).Gender,tumor differentiation and the rate of lymph nodes metastasis were independent factors affecting distant metastasis (P ＜ 0.05).The intrathoracic lymph nodes recurrence rate of upper/middle TESCC was significantly higher than that of the lower TESCC (x2 =6.179,P =0.046),while the abdomen lymph nodes recurrence rate of the lower was significantly higher than that of upper/middle TESCC (x2 =15.853,P ＜ 0.05).The recurrence rate and distant metastasis rate of stage N1 patients were significantly higher than that of N0 patients (x2 =7.764-56.495,P ＜ 0.05).The abdomen lymph nodes recurrence rate of stage N1 patients was significantly higher than that of N0 in upper TESCC (x2 =7.905,P ＜0.05).The supraclavicular and intrathoracic lymph nodes recurrence rates of stage N1 patients were significantly higher than that of N0 patients in middle TESCC (x2 =12.506,18.436,P ＜ 0.05).The supraclavicular lymph nodes,anastomosis and abdomen lymph node recurrence rates of stage N1 were significantly higher than that of N0 patients in lower TESCC (x5 =5.272,4.878,18.006,P ＜ 0.05).The anastomotic recurrence rate of stage T3+4 was higher than that of T1+2 in middle/lower TESCC (x2 =4.341,7.154,P ＜ 0.05),and the abdominal lymph nodes recurrence rate of stage T3 +4 was higher than that of T1 +2 in lower TESCC (x2 =5.366,P ＜ 0.05).Conclusions The lymphatic drainage regions for postoperative radiotherapy (PORT) are selective.We suggest that abdominal lymph nodes drainage area should be noted for the stage N1 patients with upper TESCC,and the supraclavicular lymph nodes drainage area should be noted for the N1 patients with lower TESCC.In addition,the anastomosis is suggested to be included in PORT target area for stage T3/T4 middle/lower TESCC patients.

Tangeretin inhibits neurodegeneration and attenuates inflammatory responses and behavioural deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease dementia in rats.

Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests. Deficits in working memory and object recognition function were also observed following MPTP induction. Tangeretin treatment significantly attenuated the memory deficits and improved motor functions and cognition. Immunohistochemical analysis reveals the protective effects of tangeretin against MPTP lesion-induced dopaminergic degeneration and hippocampal neuronal loss. Tangeretin reduced expression of inflammatory mediators-COX-2, iNOS-as well reduced the levels of cytokines-interleukins (IL)-IL-1ß, IL-6 and IL-2. The experimental data suggest tangeretin as an effective candidate drug with potential for prevention and treatment of neuroinflammation and dementia associated with PD.

Investigations on the antifatigue and antihypoxic effects of Paecilomyces hepiali extract.

Paecilomyces hepiali, one of the most valuable and effective Chinese medicinal herbs, possesses potential antioxidant, immunomodulatory, antitumor and anti­inflammatory properties. The present study aimed to investigate the antifatigue and antihypoxic effects of Paecilomyces hepiali extract (PHC) in a mouse model. Using a rotating rod, forced swimming and running assessment, the antifatigue activity of PHC was determined. PHC administration for 7 days had no effect on mouse horizontal or vertical movement, indicating no neurotoxicity at the selected doses was observed. Using a normobaric hypoxia, sodium nitrite toxicosis and acute cerebral ischemia assessments, PHC was confirmed to possess antihypoxic effects. PHC treatment for 7 days significantly enhanced the serum and liver levels of adenosine triphosphate, superoxide dismutase and glutathione peroxidase, prior to and following 60 min of swimming. The levels of antioxidant­associated proteins in the livers of the mice were analyzed using western blotting. PHC effectively increased the expression levels of phosphorylated (p)­5'­monophosphate (AMP)­activated protein kinase (AMPK), p­protein kinase B (AKT) and p­mammalian target of rapamycin (mTOR). The results of the present study demonstrated that PHC efficiently enhanced endurance from fatigue and had antihypoxic effects through elevation of the antioxidant capacity in the serum and liver, at least in part through the AMPK and AKT/mTOR pathways. These results indicate the potential of this natural product as an antioxidant in the treatment of fatigue, hypoxia and their associated diseases.

Study of the analgesic activities, chronic toxicity and addictive potential of Jia-Yuan-Qing pill in rats.

Jia-Yuan-Qing pill (JYQP) composed of Porcellio laevis Latreille, Corydalis Rhizoma and Radix Cynanchi Paniculati at a ratio of 9:7:7 has been found to be an effective analgesic agent. The present study aimed to evaluate the safety, addictive potential and anti-cancer pain activity of JYQP in a rat model. During the 6-month chronic toxicity test, no significant changes in general behavior, defecation, postural abnormalities, dietary or water intake or blood biochemical parameters were observed in male and female rats. Although a high dose of JYQP (5 g/kg) caused swelling of the liver, spleen and kidney in male and female rats, no pathological changes were observed in all organs examined via hematoxylin and eosin staining. The analgesic effect of JYQP on bone cancer pain was successfully confirmed in a rat model of Walker 256 cell-induced bone cancer. In contrast to morphine, in a physical dependence test, JYQP produced no withdrawal symptoms following chronic administration. The data from this study provide experimental evidence supporting the clinical use of JYQP as an effective, safe and non-addictive agent for the treatment of bone cancer pain.

Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice.

The analgesic activity of Porcellio laevis Latreille, Rhizoma Corydalis, and Radix Cynanchi Paniculati have been reported in recent years. A new formula named Jia-Yuan-Qing pill (JYQP) is therefore created by combining the three herbs at 9:7:7 ratio according to traditional Chinese theories. The present study aims to evaluate the effect of JYQP as a novel painkiller in various models. Acute toxicity test was applied to evaluate the safety of JYQP. Acetic-acid-induced writhing, hot plate test, formalin test, and naloxone-pretreated writhing test were employed to elaborate the analgesic activity of JYQP and its possible mechanism. A bone cancer pain mouse model was performed to further assess the effect of JYQP in relieving cancer pain. Test on naloxone-precipitated withdrawal symptoms was conduct to examine the physical dependence of mice on JYQP. Data revealed that JYQP reduced writhing and stretching induced by acetic acid; however, this effect could not be blocked by naloxone. JYQP specifically suppressed the phase II reaction time in formalin-treated mice; meanwhile, no analgesic effect of JYQP in hot plate test was observed, indicating that JYQP exerts analgesic activity against inflammatory pain rather than neurogenic pain. Furthermore, JYQP could successfully relieve bone cancer pain in mice. No physical dependence could be observed upon long-term administration in mice. Collectively, our present results provide experimental evidence in supporting clinical use of JYQP as an effective and safe agent for pain treatment.

Prognostic prediction of BRAF(V600E) and its relationship with sodium iodide symporter in classic variant of papillary thyroid carcinomas.

BACKGROUND: The aim of this study was to evaluate the prognosis of the classic variant of papillary thyroid carcinomas with the BRAF(V600E) mutation and 131I treatment failure in those tumors due to lower functional sodium iodide symporter expression. METHODS: 109 papillary thyroid carcinomas were associated with clinicopathologic features. The BRAF(V600E) mutation was evaluated by direct sequencing and sodium iodide symporter protein was determined by immunohistochemistry. RESULTS: We found that the BRAF(V600E) mutation was significantly associated with the classic variant of papillary thyroid carcinomas and was independent of tumor size, the presence of extrathyroid invasion and lymph node metastasis, advanced TMN stages, and a high risk of disease recurrence. Moreover, the BRAF(V600E) mutation was associated with a statistically significant lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. However, those statistically significant relationships were not found in the follicular variant of papillary thyroid carcinomas. CONCLUSIONS: The BRAF(V600E) mutation might be associated with a more aggressive phenotype and a poor prognosis, causing less NIS-mediated 131I uptake due to a lower functional NIS protein expression in the classic variant of papillary thyroid carcinomas. Our current study appears to be valuable for predicting prognosis and is of important clinical significance for surgery and 131I treatment in patients with the classic variant of papillary thyroid carcinomas.

Molecular biomarkers of colorectal cancer: prognostic and predictive tools for clinical practice.

Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.