ABSTRACT: Acute liver injury (ALI) is an important medical problem that requires effective therapy. Astaxanthin (AST) is a carotenoid, and the beneficial effects of astaxanthin, including anti-oxidative, anti-inflammatory and anti-tumour activities, have been identified. The present study was designed to elucidate the protective effects of astaxanthin against ALI and their underlying mechanisms. RAW264.7 macrophages were treated with dimethyl sulfoxide combined with different doses of astaxanthin for 12 h. Mice were fed with or without astaxanthin for up to 7 days. LPS was administered to induce inflammation. We assessed histopathology, oxidative stress, inflammation and apoptosis .The results indicated that astaxanthin attenuated LPS-induced oxidative stress, inflammation and cell apoptosis both in vivo and in vitro. In vivo and in vitro experiments showed that astaxanthin down regulated the nuclear factor-kappa beta (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2) and NLR family pyrin domain containing 3 (NLRP3) signalling pathways, inhibiting the LPS-induced inflammatory response, oxidative stress and cell apoptosis, and alleviating LPS-induced ALI in mice.

RESUMO: A lesão hepática aguda (ALI) é um problema médico importante que requer terapia eficaz. A astaxantina (AST) é um carotenóide, e os efeitos benéficos da astaxantina, incluindo atividades antioxidantes, anti-inflamatórias e antitumorais, foram identificados. O presente estudo foi desenhado para elucidar os efeitos protetores da astaxantina contra ALI e seus mecanismos subjacentes. Macrófagos RAW264.7 foram tratados com dimetil sulfóxido combinado com diferentes doses de astaxantina por 12 h. Os camundongos foram alimentados com ou sem astaxantina por até sete dias. O LPS foi administrado para induzir a inflamação. Histopatologia, estresse oxidativo, inflamação e apoptose foram avaliados. Os resultados indicaram que a astaxantina atenuou o estresse oxidativo induzido por LPS, inflamação e apoptose celular in vivo e in vitro. Experimentos in vivo e in vitro mostraram que a astaxantina regulou negativamente as vias de sinalização do fator nuclear-kappa beta (NF-κB), fator nuclear 2 relacionado ao eritróide 2 (Nrf2) e domínio de pirina da família NLR contendo 3 (NLRP3), inibindo o LPS- resposta inflamatória induzida, estresse oxidativo e apoptose celular e alívio da ALI induzida por LPS em camundongos.

ABSTRACT Purpose To investigate the effect of ferulic acid (FA) on spinal cord injury (SCI)-induced motor dysfunction and to explore the possible pharmacological mechanisms. Methods Adult male Wistar rats were used in our study. SCI was achieved by clipping the spinal cord T9 of the rat by a vascular clip for 2 minutes. The motor function of the rat was evaluated by Basso, Beattie, and Bresnahan scoring method (BBB) and inclined plane test. Hematoxylin and eosin (HE) staining, NISSL staining, and transmission electron microscopic examination were used to evaluate alterations at the histological level. Polymerase chain reaction (PCR), Western blots, and enzyme-linked immunosorbent assays (ELISA) were employed in biochemical analysis. Results The BBB score and inclined plane test score significantly decreased after SCI surgery, whereas chronic FA treatment (dose of 90 mg/kg, i.g.) for 28 days improved SCI-induced motor dysfunction. HE staining showed that SCI surgery induced internal spinal cord edema, but the structural changes of the spinal cord could be reversed by FA treatment. NISSL staining and transmission electron microscopic examination confirmed the improvement of the effect of FA on the injury site. In the biochemical analysis, it could be found that FA inhibitedSCI-induced mRNA and protein overexpression of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), as well as iNOS and COX-2 via the modulation of NF-κB level in the spinal cord of SCI rat. Moreover, the SCI-induced decrease of Bcl-2/Bax ratio was also reversed by FA treatment. However, the effect of FA on the expression of Beclin-1 was not statistically significant. Conclusions FA showed a therapeutic effect on SCI, which may be associated with the regulation of neuroinflammation and apoptosis.

OBJECTIVES: Mesenchymal stem cells (MSCs) are potentially ideal for type 2 diabetes treatment, owing to their multidirectional differentiation ability and immunomodulatory properties. Here we investigated whether the stem cells from human exfoliated deciduous teeth (SHED) in combination with hyperbaric oxygen (HBO) could treat type 2 diabetic rats, and explored the underlying mechanism. METHODS: SD rats were used to generate a type 2 diabetes model, which received stem cell therapy, HBO therapy, or both together. Before and after treatment, body weight, blood glucose, and serum insulin, blood lipid, pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), and urinary proteins were measured and compared. After 6 weeks, rats were sacrificed and their organs were subjected to hematoxylin and eosin staining and immunofluorescence staining for insulin and glucagon; apoptosis and proliferation were analyzed in islet cells. Structural changes in islets were observed under an electron microscope. Expression levels of Pdx1, Ngn3, and Pax4 mRNAs in the pancreas were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: In comparison with diabetic mice, those treated with the combination or SHE therapy showed decreased blood glucose, insulin resistance, serum lipids, and pro-inflammatory cytokines and increased body weight and serum insulin. The morphology and structure of pancreatic islets improved, as evident from an increase in insulin-positive cells and a decrease in glucagon-positive cells. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining of islet cells revealed the decreased apoptosis index, while Ki67 and proliferating cell nuclear antigen staining showed increased proliferation index. Pancreatic expression of Pdx1, Ngn3, and Pax4 was upregulated. CONCLUSION: SHED combined with HBO therapy was effective for treating type 2 diabetic rats. The underlying mechanism may involve SHED-mediated increase in the proliferation and trans-differentiation of islet β-cells and decrease in pro-inflammatory cytokines and apoptosis of islets.

OBJECTIVE: The present study aimed to investigate the relationship between obesity and mortality in patients with community-acquired pneumonia (CAP) in China. METHODS: In total, 909 patients with CAP were recruited for this study from January 2010 to June 2015. All patients were selected and divided into 4 groups according to their body mass index (BMI) values. All patients’ clinical information was recorded. The associations among mortality; BMI; the 30-day, 6-month and 1-year survival rates for different BMI classes; the etiology of pneumonia in each BMI group; and the risk factors for 1-year mortality in CAP patients were analyzed. RESULT: With the exception of the level of C-reactive protein (CRP), no other clinical indexes showed significant differences among the different BMI groups. No significant differences were observed among all groups in terms of the 30-d and 6-month mortality rates (p>0.05). There was a significantly lower risk of 1-year mortality in the obese group than in the nonobese group, (p<0.05). Logistic regression analysis showed that there were seven independent risk factors for 1-year mortality in CAP patients, namely, age, cardiovascular disease, cerebrovascular disease, obesity, APACHE II score, level of CRP and CAP severity. CONCLUSION: Compared with nonobese patients with CAP, obese CAP patients may have a lower mortality rate, especially with regard to 1-year mortality, and CRP may be associated with the lower mortality rate in obese individuals than in nonobese individuals.

Abstract Background: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. Objectives: To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Methods: Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. Results: On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05) Study limitations: The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. Conclusion: The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

RESUMO: Tal como uma molécula de sinal de gás, sulfureto de hidrogenio endógena (H2S) desempenha um papel crucial na resposta ao stress das plantas. Mas não foi relatado o papel de H2S em plantas poluentes orgânicos stress. Este estudo sobre a variação de H2S envolvido em plântulas de soja tolerância 1,4-Diclorobenzeno foi investigada. Os resultados mostraram sob o 1,4-diclorobenzeno stress, que o crescimento da soja (Glycine max) de raiz de mudas e caule foram inibidas, L- / D-cisteína desulfhydrase (LCD / DCD) atividades enzimáticas foram empossados, em seguida, H2S endógeno aumentado. Quando aplicado com hidrossulfureto de sódio (NaSH), um doador de H2S, raiz de plântulas de soja, a inibição do crescimento pode ser melhorada. Tratamentos prévios com 0,4mmol L-1 NaHS, malondialdeído (MDA) e espécies de oxigênio reactivas conteúdo (ROS) foi reduzida, em seguida, a toxicidade celular da raiz foi reduzida significativamente. Outros experimentos confirmaram que NaSH melhorou a peroxidase de plântulas de soja (POD), superóxido dismutase (SOD) atividades enzimáticas. Em contraste, estes efeitos foram revertidos por hypotaurine (HT), um eliminador de H2S. Então H2S pode aliviar toxicidade 1,4-diclorobenzeno em plântulas de soja por meio da regulamentação das atividades de enzimas antioxidantes para manter a integridade da estrutura celular.

ABSTRACT: As a gas signaling molecule, endogenous hydrogen sulfide (H2S) plays a crucial role in the plant stress response. However, the role of H2S in the response to organic pollutants specifically has not been studied. Here, the effects of H2S addition on soybean (Glycine max) seedlings tolerance of 1,4-dichlorobenzene (1,4-DCB) were investigated. Under 1,4-DCB stress, the growth of soybean seedlings roots and stems was inhibited, while L-/D-cysteine desulfhydrase (LCD/DCD) activity was induced and endogenous H2S increased. When applied jointly with sodium hydrosulfide (NaHS), a H2S donor, root growth inhibition was effectively alleviated. Pre-treatment of seedlings with 0.4mmol L-1 NaHS reduced the malondialdehyde (MDA) and reactived oxygen species (ROS) content, mitigating root cell toxicity significantly. Further experiments confirmed that NaHS enhanced soybean seedlings peroxidase (POD) and superoxide dismutase (SOD) enzyme activities. In contrast, these effects were reversed by hypotaurine (HT), a H2S scavenger. Therefore, H2S alleviated 1,4-DCB toxicity in soybean seedlings by regulating antioxidant enzyme activity to reduce cell oxidative damage.

Patrinia heterophylla Bunge, Caprifoliaceae, is a traditional Chinese medicine that has been used for cancer therapy. In our study, a panel of human cancer cells was treated with extract of Patrinia heterophylla Bunge. (PHEB), MTT study showed that PC-3 Human prostate adenocarcinoma was the most responsive (IC50 9.21±0.32 µg/mL) one to cell growth inhibition, the further study also demonstrated that PHEB could inhibit the proliferation of PC-3 based on a concentration-and time-dependent manner. The transplanted model of sarcoma 180 (S180) and hepatoma 22 (H22) was established in mice, the study demonstrated that i.p. administration of 20, 40, 60 mg/kg PHEB exhibited a significant inhibitory effect on the growth of transplantation tumor, with inhibition rate 23.9, 48.4 and 53.6% on S180 and 21.0, 46.3 and 57.2% on H22, respectively. To investigate the molecular mechanism of PHEB in PC-3, the morphological changes of apoptosis were observed by fluorescent microscopy, apoptosis rate was analyzed by flow cytometry (FCM). Morphological characterizations such as apoptotic bodies and membrane blebs were shown by microscopy. The increase of an early apoptotic population was observed in a dose-dependent manner. These results suggest that PHEB has anti-tumor effects and its mechanism is attributed partially to apoptosis induced.