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1.
Mar Drugs ; 18(4)2020 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-32244363

RESUMO

Two 11,20-epoxybriaranes, including a known compound, juncenolide K (1), as well as a new metabolite, fragilide X (2), have been isolated from gorgonian Junceella fragilis collected off the waters of Taiwan. The absolute configuration of juncenolide K (1) was determined by single-crystal X-ray diffraction analysis for the first time in this study and the structure, including the absolute configuration of briarane 2 was established on the basis of spectroscopic analysis and compared with that of model compound 1. One aspect of the stereochemistry of the known compound 1 was revised. Briarane 2 was found to enhance the generation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) release from RAW 264.7 cells.

2.
Zhen Ci Yan Jiu ; 45(1): 46-50, 2020 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-32144908

RESUMO

OBJECTIVE: To observe the clinical effect of herbal cake-partitioned moxibustion combined with Rhinocort spray in the treatment of symptoms, sleep quality and daily life quality of patients with moderate-severe allergic rhinitis(AR).. METHODS: A total of 67 patients with persistent moderate-severe AR were recruited in the present study and randomized into a treatment group (n=35) and a control group (n=32). The patients in the treatment group were treated by herbal cake-partitioned moxibustion (applied to Dazhui [GV14], and bilateral Feishu [BL13], Shenshu [BL23] and Zhiyang [GV9], 3 moxa-cones/time, once every other day) plus Rhinocort spray (once in the morning and evening separately, 256 µg/d), and patients in the control group treated by Rhinocort spray alone (the same to that mentioned above). All the treatments were given for 4 weeks. The therapeutic effect was evaluated with reference to the "Principles and Recommended Schemes for Diagnosis and Treatment of AR" formulated by Otolaryngology Branch of Chinese Medical Association before and after the treatment. The severity of symptoms of AR was assessed by using visual analogue scale (VAS), the life quality of nasal conjunctivitis assessed using "Rhino-conjunctivitis Quality of Life Questionnaire (RQLQ)", and the sleep quality assessed using "Pittsburgh Sleep Quality Index (PSQI)" before and after the treatment, followed by 3 months' follow-up survey. RESULTS: After the treatment, the VAS and RQLQ scores in both groups and PSQI of the treatment group were significantly decreased in comparison with their own base-line levels of pre-treatment in each group (P<0.05). The RQLQ and PSQI in the treatment group were substantially lower than those in the control group (P<0.05). No marked difference was found between the two groups in VAS(P>0.05). Follow-up survey showed that the VAS and RQLQ scores in both groups and PSQI of the treatment group were still significantly lower than those of pre-treatment in each group(P<0.05), and the VAS, RQLQ and PSQI scores of the treatment group were significantly lower than those of the control group(P<0.05). After 4 weeks' treatment, of the 32 and 35 AR patients in the control and treatment groups, 7 and 16 experienced marked improvement, 16 and 14 were effective, and 9 and 5 failed, with the effective rate being 71.9% and 85.7%, respectively. The effective rate of the treatment group was significantly superior to that of the control group (P<0.05). CONCLUSION: Herbal cake-partitioned moxibustion combined with Rhinocort spray has a good therapeutic effect in improving symptoms, sleep and quality of life in patients with persistent moderate-severe AR, which is obviously superior to that of Rhinocort spray alone in improving sleep and quality of life.


Assuntos
Moxibustão , Rinite Alérgica , Pontos de Acupuntura , Budesonida , Humanos , Qualidade de Vida , Rinite Alérgica/terapia
3.
J Nanosci Nanotechnol ; 20(8): 5162-5174, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126717

RESUMO

This study aimed to develop emulsification assisted with ultrasonic atomization (EUA) to make embolic biodegradable poly(caprolactone) (PCL) spherical-microcarriers with uniform particle size for mass production which was used to cure hepatocellular carcinoma, because this kind of embolic drugs is expensive at the current market due to their complex manufacturing process. The embolic spherical-microcarriers with sustained-releasing therapeutic agents can shrink an unresectable tumor into a respectable size. Through high frequency vibrating surface on the ultrasonic atomizer nozzle, the thin liquid film for PCL oil-phase solution was broken into the uniform PCL microdroplets (particle sizes are from 20 to 55 µm) with less medicine loss. To determine the optimal parameters to make PCL microcarriers, the ultrasonic module parameters including the concentration of PCL solution, vibrating amplitude of atomizer, feeding rate of PCL oil-phase solution and collection distance on the particle size of microdroplets were analyzed. Besides, a vertical circulation flow field of aqueous-phase poly(vinyl alcohol) (PVA) solution was created to enhance the separation of the microdroplets and increase the production of the PCL microcarriers, and about 8~11 wt% of PVA solution with high stable dispersion property was used to effectively improve the yield rate of PCL spherical-microcarriers (89.8~98.2 wt%). The final particle size of PCL microcarriers was ca. 5-18 µm, indicating an about 25-50% volume shrinkage from microdroplets to solid spherical-microcarriers.

4.
Molecules ; 25(6)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204524

RESUMO

Five 8,17-epoxybriaranes, including three new compounds-briarenols I-K (1-3), along with two known analogues, briaexcavatolide P (4) and briaexcavatin P (5), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1-3 were elucidated by spectroscopic methods, including 1D and 2D NMR studies and (+)-HRESIMS. Briarane 4 exerted inhibition effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) release from RAW 264.7.

5.
Sci Rep ; 10(1): 5045, 2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32193508

RESUMO

Osteosarcoma (OSA) is the most common type of cancer that originates in the bone and usually occurs in young children. OSA patients were treated with neoadjuvant chemotherapy and surgery, and the results were disappointing. Marine antimicrobial peptides (AMPs) have been the focus of antibiotic research because they are resistant to pathogen infection. Piscidin-1 is an AMP from the hybrid striped bass (Morone saxatilis × M. chrysops) and has approximately 22 amino acids. Research has shown that piscidin-1 can inhibit bacterial infections and has antinociception and anti-cancer properties; however, the regulatory effects of piscidin-1 on mitochondrial dysfunction in cancer cells are still unknown. We aimed to identify the effects of piscidin-1 on mitochondrial reactive oxygen species (mtROS) and apoptosis in OSA cells. Our analyses indicated that piscidin-1 has more cytotoxic effects against OSA cells than against lung and ovarian cancer cells; however, it has no effect on non-cancer cells. Piscidin-1 induces apoptosis in OSA cells, regulates mtROS, reduces mitochondrial antioxidant manganese superoxide dismutase and mitochondrial transmembrane potential, and decreases adenosine 5'-triphosphate production, thus leading to mitochondrial dysfunction and apoptosis. The mitochondrial antioxidant, mitoTempo, reduces the apoptosis induced by piscidin-1. Results suggest that piscidin-1 has potential for use in OSA treatment.

6.
Food Chem Toxicol ; 135: 110993, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765702

RESUMO

3S, 3'S-Astaxanthin is the most powerful antioxidant to scavenge free radicals in the world. In this study, a 3S, 3'S-astaxanthin biosynthesis pathway was constructed in a probiotic yeast, Kluveromyces marxianus, denoted YEAST, and its bioactive metabolites were extracted for biofunctional assessments. The bio-safety examination was achieved by two animal models as following: First, no significant toxic effects on YEAST groups were found in zebrafish; Second, after feeding YEAST for 4 weeks, the rat-groups showed no visible abnormality, and no significant change of the body weight and blood biochemistry tests. The inhibition of lung metastasis of melanoma cells and the increment of the survival rate were demonstrated by feeding YEAST and injecting the intravenous commercial astaxanthin in vivo rodent model. Based on in vitro assays of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging analysis, ferrous ion chelating ability, reducing power assessment, and mushroom tyrosinase inhibition evaluation, YEAST-astaxanthin showed anti-oxidative and tyrosinase suppressive properties. Taken together, the 3S, 3'S-astaxanthin producing probiotic yeast is safe to be used in the bio-synthesis of functional and pharmaceutical compounds, which have broad industrial applications on cosmetic, food and feed additive and healthcare.


Assuntos
Kluyveromyces/metabolismo , Melanoma Experimental/patologia , Engenharia Metabólica , Metástase Neoplásica/prevenção & controle , Probióticos , Animais , Antioxidantes/farmacologia , Feminino , Masculino , Melanoma Experimental/enzimologia , Camundongos , Camundongos Endogâmicos BALB C , Monofenol Mono-Oxigenase/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Xantofilas/química , Xantofilas/metabolismo , Xantofilas/farmacologia , Peixe-Zebra
7.
Eur J Pain ; 24(1): 209-222, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31495059

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most common joint disease, especially affecting the knee joint. Etoricoxib, a highly selective cyclooxygenase (COX)-2 inhibitor which can reduce postoperative pain after orthopaedic surgery. The aim of this study was to investigate the effects of oral etoricoxib on the development of OA and to examine concomitant changes in the nociceptive behaviour of rats. METHOD: OA was induced in wistar rats by anterior cruciate ligament transection (ACLT) of the right knee. The ACLT + etoricoxib groups received 6.7 or 33.3 mg/kg of oral etoricoxib three times a week for 12 consecutive weeks, starting at week 8 after ACLT. Nociceptive behaviours and changes in knee joint width during OA development were analyzed. Histopathological studies were then performed on the cartilage. Immunohistochemical analysis was performed to examine the effect of etoricoxib on the expression of transforming growth factor-beta (TGF-ß) and nerve growth factor (NGF) in articular cartilage chondrocytes. RESULTS: OA rats receiving etoricoxib showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Nociceptive behaviour studies showed significant improvement in the ACLT + etoricoxib groups compared to that in the ACLT group. Moreover, etoricoxib attenuated NGF expression, but increased TGF-ß expression, in OA-affected cartilage. CONCLUSIONS: Oral etoricoxib in a rat OA model (a) attenuates the development of OA, (b) concomitantly reduces nociception, and (c) modulates chondrocyte metabolism, possibly by inhibiting NGF expression and increasing TGF-ß expression. SIGNIFICANCE: Oral administration of etoricoxib can attenuate the development of OA, with an associated attenuation of nociceptive behaviour in an experimental rat OA model. Moreover, etoricoxib attenuated NGF expression, but enhanced TGF-ß expression in OA-affected chondrocytes. These findings may pave the way for further investigations of etoricoxib as a potential therapeutic target for the treatment of the inflammatory component in OA.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31803144

RESUMO

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria. Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared. Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group. Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

9.
Sci Rep ; 9(1): 18851, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827193

RESUMO

Coral reefs are suffering on a global scale due to human impacts, thereby necessitating cryopreservation efforts. The objective of this study was to develop a suitable vitrification and laser warming protocol for larvae of the scleractinian coral Seriatopora caliendrum, which inherit their dinoflagellate algal symbionts vertically. Toxicity experiments were conducted with the cryoprotectants (CPAs) ethylene glycol (EG), propylene glycol (PG), dimethyl sulfoxide (DMSO), glycerol (GLY), and methanol (METH; listed in order from least to most toxic), and larvae were subjected to vitrification and laser warming using 2 M EG + 1 M PG and 2 M EG + 1 M DMSO. Vitrification and laser warming (300 V, 10 ms pulse width, 2 mm beam diameter) using a vitrification solution of 2 M EG + 1 M PG, 40% w/v Ficoll, and 10% v/v gold nanobars (GNB) at a final concentration of 1.2 × 1018 GNB/mL and a characteristic wavelength of 535 nm resulted in larvae with vitality and settlement percentages of 55 and 9%, respectively. This represents the first successful instance of cryopreservation of coral larvae that proceeded to settle upon warming, and suggests that the vitrification and ultra-fast laser warming approach may be applicable to other threatened marine species.

10.
Mar Drugs ; 17(12)2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31847481

RESUMO

Three new 11,20-epoxybriaranes-fragilides U-W (1-3), as well as two known metabolites, junceellonoid D (4) and junceellin (5), were obtained from the octocoral Junceella fragilis. The structures of briaranes 1-3 were elucidated by spectroscopic methods and briaranes 3 and 5 displayed inhibition effects on inducible nitric oxide synthase (iNOS) release from RAW264.7.

11.
Mar Drugs ; 17(11)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671563

RESUMO

Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction and finally death. LPS challenge-induced inflammatory responses during sepsis may increase the likelihood of the arrhythmogenesis. Lemnalol is known to possess potent anti-inflammatory effects. This study examined whether Lemnalol (0.1 µM) could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes under the influence of LPS (1µg/mL). Under challenge with LPS, Lemnalol-treated LA myocytes, had a longer AP duration at 20%, 50% and 90% repolarization of the amplitude, compared to the LPS-treated cells. LPS-challenged LA myocytes showed increased late sodium current, Na+-Ca2+ exchanger current, transient outward current, rapid component of delayed rectifier potassium current, tumor necrosis factor-α, NF-κB and increased phosphorylation of ryanodine receptor (RyR), but a lower L-type Ca2+ current than the control LA myocytes. Exposure to Lemnalol reversed the LPS-induced effects. The LPS-treated and control groups of LA myocytes, with or without the existence of Lemnalol. showed no apparent alterations in the sodium current amplitude or Cav1.2 expression. The expression of sarcoendoplasmic reticulum calcium transport ATPase (SERCA2) was reduced by LPS treatment, while Lemnalol ameliorated the LPS-induced alterations. The phosphorylation of RyR was enhanced by LPS treatment, while Lemnalol attenuated the LPS-induced alterations. In conclusion, Lemnalol modulates LPS-induced alterations of LA calcium homeostasis and blocks the NF-κB pathways, which may contribute to the attenuation of LPS-induced arrhythmogenesis.

12.
Theranostics ; 9(22): 6631-6645, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588240

RESUMO

Rationale: Tumor angiogenesis promotes tumor development, progression, growth, and metastasis. Metronomic chemotherapy involves the frequent administration of low-dose chemotherapeutic agents to block angiogenic activity and reduce side effects. Methods: MDA-MB-231 cells were treated with various concentrations of artemisinin (ART) and vinorelbine (NVB) and the cytotoxic effects of ART/NVB were determined using the CCK-8 assay. Mitochondrial reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆Ψm) and mass were assessed using MitoSOX, TMRE and MitoTracker green staining. Western blot analysis was used to quantify the expression of autophagy-related proteins. Herein, by using bioinformatics analysis and experimental verification, we identified CREB as a master in MDA-MB-231 cells. Results: We found that artemisinin (ART), which exhibits anti-angiogenic and anti-cancer effects via mitochondrial regulation, synergized with vinorelbine (NVB) to inhibit MDA-MB-231 cell proliferation. ART and NVB cooperated to regulate mitochondrial biogenesis. CREB acted as a crucial regulator of PGC1α and VEGF, which played critical roles in NVB-dependent growth factor depletion. Moreover, CREB suppression significantly reversed mitochondrial dysfunction following ART/NVB co-treatment. In addition, combination treatment with ART and NVB significantly suppressed tumor growth in a nude mouse xenograft model, with downregulated CREB and PGC1α expression levels observed in tumor biopsies, in agreement with our in vitro and ex vivo data. Conclusions: These findings support the hypothesis that ART affects cancer and endothelial cells by targeting the auto-paracrine effects of VEGF to suppress mitochondrial biogenesis, angiogenesis, and migration between cancer cells and endothelial cells.

13.
Curr Pharm Des ; 25(24): 2637-2649, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603057

RESUMO

BACKGROUND: Multimodal imaging plays an important role in the diagnosis of brain disorders. Neurological disorders need to be diagnosed at an early stage for their effective treatment as later, it is very difficult to treat them. If possible, diagnosing at an early stage can be much helpful in curing the disease with less harm to the body. There is a need for advanced and multimodal imaging techniques for the same. This paper provides an overview of conventional as well as modern imaging techniques for brain diseases, specifically for tumor imaging. In this paper, different imaging modalities are discussed for tumor detection in the brain along with their advantages and disadvantages. Conjugation of two and more than two modalities provides more accurate information rather than a single modality. They can monitor and differentiate the cellular processes of normal and diseased condition with more clarity. The advent of molecular imaging, including reporter gene imaging, has opened the door of more advanced noninvasive detection of brain tumors. Due to specific optical properties, semiconducting polymer-based nanoparticles also play a pivotal role in imaging tumors. OBJECTIVE: The objective of this paper is to review nanoparticles-mediated brain imaging and disease prognosis by conventional as well as modern modal imaging techniques. CONCLUSION: We reviewed in detail various medical imaging techniques. This paper covers recent developments in detail and elaborates a possible research aspect for the readers in the field.

14.
Sci Rep ; 9(1): 12633, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477754

RESUMO

Lung injury is one of the pathological hallmarks of most respiratory tract diseases including asthma, acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD). It involves progressive pulmonary tissue damages which are usually irreversible and incurable. Therefore, strategies to facilitate drug development against lung injury are needed. Here, we characterized the zebrafish folate-deficiency (FD) transgenic line that lacks a fully-developed swim bladder. Whole-mount in-situ hybridization revealed comparable distribution patterns of swim bladder tissue markers between wild-type and FD larvae, suggesting a proper development of swim bladder in early embryonic stages. Unexpectedly, neutrophils infiltration was not observed in the defective swim bladder. Microarray analysis revealed a significant increase and decrease of the transcripts for cathepsin L and a cystatin B (CSTB)-like (zCSTB-like) proteins, respectively, in FD larvae. The distribution of cathepsin L and the zCSTB-like transcripts was spatio-temporally specific in developing wild-type embryos and, in appropriate measure, correlated with their potential roles in maintaining swim bladder integrity. Supplementing with 5-formyltetrahydrofolate successfully prevented the swim bladder anomaly and the imbalanced expression of cathepsin L and the zCSTB-like protein induced by folate deficiency. Injecting the purified recombinant zebrafish zCSTB-like protein alleviated FD-induced swim bladder anomaly. We concluded that the imbalanced expression of cathepsin L and the zCSTB-like protein contributed to the swim bladder malformation induced by FD and suggested the potential application of this transgenic line to model the lung injury and ECM remodeling associated with protease/protease inhibitor imbalance.

15.
Mar Drugs ; 17(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514359

RESUMO

Two new steroids, dendronesterones D (1) and E (2), featuring with 1,4-dienone moiety, along with three known steroids, methyl 3-oxochola-4,22-diene-24-oate (3), 5α,8α-epidioxy-24(S)- methylcholesta-6,22-dien-3ß-ol (4), and 5α,8α-epidioxy-24(S)-methylcholesta-6,9(11),22-trien-3ß-ol (5), were isolated from an octocoral Dendronephthya sp. The structures of steroids 1 and 2 were elucidated by using spectroscopic methods and steroid 1 was found to exhibit significant in vitro anti-inflammatory activity in lipopolysaccharides (LPS)-induced RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein.


Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Esteroides/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Células RAW 264.7 , Esteroides/isolamento & purificação
16.
Mar Drugs ; 17(9)2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540107

RESUMO

Three new 8-hydroxybriaranes-fragilides R-T (1-3) were obtained from a sea whip gorgonian coral Junceella fragilis. The structures of briaranes 1-3 were elucidated by using spectroscopic methods, including 1D (1H and 13C NMR), 2D (COSY, HSQC, HMBC, and NOESY experiments) NMR studies, and (+)-HRESIMS. Fragilides S and T (2 and 3) are the only briaranes known to possess 8α-hydroxy and 17ß-methyl groups, respectively. Briarane 2 exerted an inhibition effect on iNOS release from RAW264.7; a macrophage cell line that originated from a mouse monocyte macrophage, stimulated with lipopolysaccharides.


Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Células RAW 264.7 , Relação Estrutura-Atividade
17.
Front Neurosci ; 13: 769, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440123

RESUMO

Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases, and neuroinflammation has been identified as one of its key pathological characteristics. Triggering receptors expressed on myeloid cells-1 (TREM-1) amplify the inflammatory response and play a role in sepsis and cancer. Recent studies have demonstrated that the attenuation of TREM-1 activity produces cytoprotective and anti-inflammatory effects in macrophages. However, no study has examined the role of TREM-1 in neurodegeneration. We showed that LP17, a synthetic peptide blocker of TREM-1, significantly inhibited the lipopolysaccharide (LPS)-induced upregulation of proinflammatory cascades of inducible nitric oxide synthase (iNOS), cyclooxygenase-2, and nuclear factor-kappa B. Moreover, LP17 enhanced the LPS-induced upregulation of autophagy-related proteins such as light chain-3 and histone deacetylase-6. We also knocked down TREM-1 expression in a BV2 cell model to further confirm the role of TREM-1. LP17 inhibited 6-hydroxydopamine-induced locomotor deficit and iNOS messenger RNA expression in zebrafish. We also observed therapeutic effects of LP17 administration in 6-hydroxydopamine-induced PD syndrome using a rat model. These data suggest that the attenuation of TREM-1 could ameliorate neuroinflammatory responses in PD and that this neuroprotective effect might occur via the activation of autophagy and anti-inflammatory pathways.

18.
Oncogene ; 38(37): 6461-6477, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31332288

RESUMO

Helicobacter pylori (Hp) infection and overexpression of hepatoma-derived growth factor (HDGF) are involved in gastric carcinogenesis. However, the relationship between Hp-induced gastric diseases and HDGF upregulation is not yet completely clear. This study aimed to elucidate the role of HDGF in Hp-induced gastric inflammation and carcinogenesis. HDGF expression in gastric biopsy and serum from patients was analyzed by immunohistochemical and ELISA analysis, respectively. Hp and gastric cells coculture system was employed to delineate the mechanism underlying HDGF overexpression during Hp infection. The gastric pathologies of wild type and HDGF knockout mice after Hp infection were investigated by immunohistochemical, immunoblot, and immunofluorescence analyses. HDGF level was significantly elevated in patients with Hp infection or intestinal metaplasia (IM, a precancerous lesion), and HDGF overexpression was positively correlated with Hp load, IM, and neutrophil infiltration in gastric biopsy. Consistently, patients with Hp infection or IM had significantly higher serum HDGF level. By using coculture assay, Hp infection led to HDGF upregulation and secretion in gastric cells. In mice model, HDGF ablation significantly suppressed the Hp-induced neutrophil infiltration and inflammatory TNF-α/COX-2 signaling, thereby relieving the tissue damage in stomach. This was further supported by that recombinant HDGF (rHDGF) stimulated the differentiation/chemotaxis of cultured neutrophils and oncogenic behaviors of gastric cells. Time series studies showed that Hp infection elicited an inflammatory TNF-α/HDGF/COX-2 cascade in stomach. HDGF secretion by Hp infection promotes the neutrophils infiltration and relays Hp-induced inflammatory signaling. Thus, HDGF may constitute a novel diagnostic marker and therapeutic target for Hp-induced gastritis and carcinogenesis.


Assuntos
Gastrite , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Infiltração de Neutrófilos , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Animais , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Células Cultivadas , Mucosa Gástrica/imunologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Gastrite/genética , Gastrite/imunologia , Gastrite/microbiologia , Gastrite/patologia , Células HL-60 , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Estômago/imunologia , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia
19.
Ecotoxicol Environ Saf ; 182: 109380, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31279279

RESUMO

Ultraviolet (UV) is an omnipresent environmental carcinogen transmitted by sunlight. Excessive UV irradiation has been correlated to an increased risk of skin cancers. UVB, the most mutagenic component among the three UV constituents, causes damage mainly through inducing DNA damage and oxidative stress. Therefore, strategies or nutrients that strengthen an individual's resistance to UV-inflicted harmful effects shall be beneficial. Folate is a water-soluble B vitamin essential for nucleotides biosynthesis, and also a strong biological antioxidant, hence a micronutrient with potential of modulating individual's vulnerability to UV exposure. In this study, we investigated the impact of folate status on UV sensitivity and the protective activity of folate supplementation using a zebrafish model. Elevated reactive oxygen species (ROS) level and morphological injury were observed in the larvae exposed to UVB, which were readily rescued by supplementing with folic acid, 5-formyltetrahydrofolate (5-CHO-THF) and N-acetyl-L-cysteine (NAC). The UVB-inflicted abnormalities and mortality were worsened in Tg(hsp:EGFP-γGH) larvae displaying folate deficiency. Intriguingly, only supplementation with 5-CHO-THF, as opposed to folic acid, offered significant and consistent protection against UVB-inflicted oxidative damage in the folate-deficient larvae. We concluded that the intrinsic folate status correlates with the vulnerability to UVB-induced damage in zebrafish larvae. In addition, 5-CHO-THF surpassed both folic acid and NAC in preventing UVB-inflicted oxidative stress and injury in our current experimental zebrafish model.


Assuntos
Deficiência de Ácido Fólico/prevenção & controle , Leucovorina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Complexo Vitamínico B/farmacologia , Peixe-Zebra/metabolismo , Acetilcisteína/farmacologia , Animais , Antioxidantes/farmacologia , Suplementos Nutricionais , Deficiência de Ácido Fólico/metabolismo , Larva/efeitos dos fármacos , Larva/metabolismo , Estresse Oxidativo/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo
20.
Molecules ; 24(13)2019 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-31284657

RESUMO

Two new 11,20-epoxybriaranes, fragilides P (1) and Q (2), as well as two known analogues, robustolide F (3) and juncin Z (4), were obtained from the gorgonian coral Junceella fragilis. The structures, including the absolute configurations of briaranes 1 and 2, were elucidated by using spectroscopic methods and comparing the spectroscopic and rotation data with those of known related analogues. Briarane 4 decreased the generation of superoxide anions by human neutrophils. The propionate group in 1 is rarely found.


Assuntos
Antozoários/química , Diterpenos/química , Proteínas de Plantas/química , Animais , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Proteínas de Plantas/isolamento & purificação , Proteínas de Plantas/farmacologia , Análise Espectral
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