Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Low-cost Prussian blue analogues for sodium-ion batteries and other metal-ion batteries.

As a class of promising cathodes in the field of large-scale power storage systems especially for alkali-metal-ion batteries (MIBs), Prussian blue (PB) and its analogues (PBAs) have received wide research attention due to their open framework, high theoretical specific capacity, and simple synthesis method. For large-scale applications, cathode materials with low-cost and long cycle life are preferred. However, only a few of the review papers have concentrated on the detailed analysis of low-cost PBAs, including Fe-based and Mn-based PBAs, which also show excellent electrochemical performance. This review aims to first provide an all-sided understanding of low-cost PBAs in terms of their application and recent progress in MIBs. Then, the major challenges such as inferior electrochemical properties of low-cost PBAs are discussed. Meanwhile, we provide feasible strategies to prepare PBA electrodes with advanced electrochemical performance. Finally, we present some personal perspectives and guidance for future research, aiming to narrow the gap between laboratory investigation and practical application.

CY-09 Alleviates the Depression-like Behaviors via Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation in Lipopolysaccharide-Induced Mice.

Depression is a serious mental illness, mainly characterized as large mood swings and sleep, diet, and cognitive function disorders. NLPR3, one of the inflammasomes that can be activated by a variety of stimuli to promote the maturation and secretion of pro-inflammatory cytokines, has been considered to be involved in the pathophysiology of depression. In this study, the putative role of CY-09, a selective and direct inhibitor of NLRP3, was evaluated in the lipopolysaccharide (LPS)-induced mice. The results of the study indicated that CY-09 significantly decreased the levels of NLRP3 in the hippocampus of LPS-induced mice. In addition, CY-09 increased the sucrose preference and shortened the immobility time in LPS-induced mice, suggesting the antidepressant-like effects of inhibiting NLRP3 inflammasome. Biochemical analysis showed that LPS significantly activated the NLRP3/ASC/cytokine signaling pathway and caused microglial activation, while CY-09 prevented the changes. Moreover, CY-09 increased the brain-derived neurotrophic factor (BDNF) only in microglia but not in the whole hippocampus. Meanwhile, CY-09 did not promote neurogenesis in the hippocampus of LPS mice. In conclusion, the results of the study showed that the antidepressant-like effects of NLRP3 inhibitor CY-09 were mediated by alleviating neuroinflammation in microglia and independent of the neurotrophic function in the hippocampus.

Possible Neuropathology of Sleep Disturbance Linking to Alzheimer's Disease: Astrocytic and Microglial Roles.

Sleep disturbances not only deteriorate Alzheimer's disease (AD) progress by affecting cognitive states but also accelerate the neuropathological changes of AD. Astrocytes and microglia are the principal players in the regulation of both sleep and AD. We proposed that possible astrocyte-mediated and microglia-mediated neuropathological changes of sleep disturbances linked to AD, such as astrocytic adenosinergic A1, A2, and A3 regulation; astrocytic dopamine and serotonin; astrocyte-mediated proinflammatory status (TNFα); sleep disturbance-attenuated microglial CX3CR1 and P2Y12; microglial Iba-1 and astrocytic glial fibrillary acidic protein (GFAP); and microglia-mediated proinflammatory status (IL-1b, IL-6, IL-10, and TNFα). Furthermore, astrocytic and microglial amyloid beta (Aß) and tau in AD were reviewed, such as astrocytic Aß interaction in AD; astrocyte-mediated proinflammation in AD; astrocytic interaction with Aß in the central nervous system (CNS); astrocytic apolipoprotein E (ApoE)-induced Aß clearance in AD, as well as microglial Aß clearance and aggregation in AD; proinflammation-induced microglial Aß aggregation in AD; microglial-accumulated tau in AD; and microglial ApoE and TREM2 in AD. We reviewed astrocytic and microglial roles in AD and sleep, such as astrocyte/microglial-mediated proinflammation in AD and sleep; astrocytic ApoE in sleep and AD; and accumulated Aß-triggered synaptic abnormalities in sleep disturbance. This review will provide a possible astrocytic and microglial mechanism of sleep disturbance linked to AD.

Comprehensive Analysis of Secondary Metabolites in the Extracts from Different Lily Bulbs and Their Antioxidant Ability.

The genus Lilium contains more than 100 wild species and numerous hybrid varieties. Some species of them have been used as medicine and food since ancient times. However, the research on the active components and the medical properties of lilies has only focused on a few species. In this study, the total phenolic acid content (TPC), total flavonoid content (TFC), and antioxidant capacity of 22 representative lilies were systematically investigated. The results showed that the TPC, TFC and antioxidant activity were highly variable among different lilies, but they were significantly positively correlated. Hierarchical cluster analysis indicated that L. henryi and L. regale were arranged in one group characterized by the highest TPC, TFC and antioxidant capacity, followed by Oriental hybrids and Trumpet and Oriental hybrids. The traditional edible and medicinal lilies were clustered in low TPC, TFC and antioxidant capacity group. A total of 577 secondary metabolites, including 201 flavonoids, 153 phenolic acids, were identified in the five species with great differences in antioxidant capacity by extensive targeted metabonomics. Differentially accumulated metabolites (DAMs) analysis reviewed that the DAMs were mainly enriched in secondary metabolic pathways such as isoflavonoid, folate, flavonoid, flavone, flavonol, phenylpropanoid, isoquinoline alkaloid biosynthesis, nicotinate and nicotinamide metabolism and so on. Correlation analysis identified that 64 metabolites were significantly positively correlated with antioxidant capacity (r ≥ 0.9 and p < 0.0001). These results suggested that the genus Lilium has great biodiversity in bioactive components. The data obtained greatly expand our knowledge of the bioactive constituents of Lilium spp. Additionally, it also highlights the potential application of Lilium plants as antioxidants, functional ingredients, cosmetic products and nutraceuticals.

Anti-apoptotic and pro-survival effect of exercise training on early aged hypertensive rat cerebral cortex.

The anti-apoptotic and pro-survival effects of exercise training were evaluated on the early aged hypertensive rat cerebral cortex. The brain tissues were analysed from ten sedentary male Wistar Kyoto normotensive rats (WKY), ten sedentary spontaneously 12 month early aged hypertensive rats (SHR), and ten hypertensive rats undergoing treadmill exercise training (60 min/day, 5 days/week) for 12 weeks (SHR-EX). TUNEL-positive apoptotic cells, the expression levels of endonuclease G (EndoG) and apoptosis-inducing factor (AIF) (caspase-independent apoptotic pathway), Fas ligand, Fas death receptor, tumor necrosis factor (TNF)-α, TNF receptor 1, Fas-associated death domain, active caspase-8 and active caspase-3 (Fas-mediated apoptotic pathways) as well as t-Bid, Bax, Bak, Bad, cytochrome c, active caspase 9 and active caspase-3 (mitochondria-mediated apoptotic pathways) were reduced in SHR-EX compared with SHR. Pro-survival Bcl2, Bcl-xL, p-Bad, 14-3-3, insulin-like growth factor (IGF)-1, pPI3K/PI3K, and pAKT/AKT were significantly increased in SHR-EX compared to those in SHR. Exercise training suppressed neural EndoG/AIF-related caspase-independent, Fas/FasL-mediated caspase-dependent, mitochondria-mediated caspase-dependent apoptotic pathways as well as enhanced Bcl-2 family-related and IGF-1-related pro-survival pathways in the early aged hypertensive cerebral cortex. These findings indicated new therapeutic effects of exercise training on preventing early aged hypertension-induced neural apoptosis in cerebral cortex.

Experience in surgical treatment of type â ¡ odontoid fractures: A report of two cases and review of the literature.

Two cases of type Ⅱ odontoid fractures were reported to share our experience in surgery treatment of such cases. A 33-year-old woman with comminuted type Ⅱ odontoid fracture and a 42-year-old man with fracture end hardened type Ⅱ odontoid fracture received surgical treatment in our hospital. Though imaging examination suggested that these two patients were suitable for anterior screw fixation, we encountered difficulties during the operation. The two patients eventually underwent posterior C1-C2 fusion surgery and recovered well. According to the experience of these two cases, we found that the fracture line angle and the degree of comminution are two important factors affecting surgical decision-making. Although anterior screw fixation is the ideal choice for type Ⅱ odontoid fractures with anterior superior to posterior inferior fracture line, it may not be the best choice for comminuted or fracture end hardened type Ⅱ odontoid fractures.

Identification of a Missense Mutation in the Surfactant Protein A2 Gene in a Chinese Family with Interstitial Lung Disease.

Interstitial lung disease (ILD) is a large group of disorders, most of which lead to progressive scarring of lung tissue. The scarring associated with ILD eventually affects your ability to breathe and get enough oxygen into your bloodstream. The typical symptoms of ILD are shortness of breath at rest or aggravated by exertion and dry cough. In this study, we enrolled a family with ILDs from central south region of China. Three patients suffered from repeated cough and shortness of breath. The high resolution computed tomography (HRCT) testing further confirmed the diagnosis of interstitial lung lesions. Whole exome sequencing (WES) and Sanger sequencing were applied to detect the genetic lesion of the family. By employing WES, a novel heterozygous mutation (NM_001098668: c.554C>T/p.A185V) of surfactant protein A2 (SFTPA2) was identified in the affected individuals and absent in the healthy members. Bioinformatics analysis predicted that this mutation is disease-causing mutation and located in an evolutionarily conserved site of SFTPA2 protein. The novel mutation may disrupt the stability of SFTPA2 protein and induce endoplasmic reticulum stress, finally leading to ILD under the influence of microorganisms. Our study not only expands the spectrum of SFTPA2 mutations but also helps the family members to mitigate ILD risk factors. The study also supplements and improves genetic testing strategies and ILD risk estimation methodologies for China.

[Characteristics and Environmental Impacts of Materials Stored in Municipal Solid Waste Landfills: A Case Study of the Guangdong-Hong Kong-Macao Greater Bay Area].

The composition of municipal solid waste (MSW) in landfills is complex; additionally, the waste stored in landfills continues to generate greenhouse gases, odors, and ground water pollutants even during the post-closure stage. Therefore, landfills are considered key fields of urban eco-environmental remediation. In this context, it is crucial to understand the storage, composition, physical, and chemical characteristics of waste, as well as its potential environmental impacts. However, very few studies have discussed these topics in detail. In this work, we focused on the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), which has the highest urbanization rate and population density of all China. The generation, stock, physical components, and key elements of MSW in eleven cities of the GBA were analyzed based on both the scientific literature and statistical data. The main results are as follows:① the total amount of MSW produced by the cities was of 26.4 Tg in 2017, with an average annual increment of 0.8 Tg; moreover, the most used disposal method was the sanitary landfill (58.9% of the total); ② the total amount of MSW disposed in the landfills was equal to 230.1 Tg[including mainly food waste (109.6 Tg), plastic (38.9 Tg), and paper (29.6 Tg)]; ③ between 2001-2017, a total of 50.0 Tg of carbon were input in the landfills in the form MSW, of which 7.1 Tg of carbon were emitted as gas and 1.5 Tg were discharged as leachate; moreover, the total landfill carbon stock was equal to 41.4 Tg. Overall, this study provides fundamental data that can be used to determine the environmental impacts of MSW landfills and implement the eco-environmental remediation of urban landfill sites in the GBA.

Min-invasive surgical treatment for multiple axis fractures: A case report.

BACKGROUND: Fractures of the axis are commonly seen in spinal injuries. Upper cervical fractures are usually managed conservatively. However, the complications due to long-term external immobilization cannot be ignored. The traditional open surgery has the disadvantages of too much blood loss and soft tissue injury. The aim of our paper is to introduce a minimally invasive surgical treatment for multiple axis fractures. CASE SUMMARY: We report a 40-year-old Chinese male who had severe neck pain and difficult neck movement after falling from 3 meters. X-ray and computed tomography (CT) scan revealed an axis injury consisting of an odontoid Type III fracture associated with a Hangman fracture categorized as a Levine-Edwards Type I fracture. The patient underwent anterior odontoid screw fixation and posterior percutaneous screw fixation using intraoperative O-arm navigation. Neck pain was markedly improved after surgery. X-rays and CT scan reconstructions of 3-mo follow-up showed good stability and fusion. The range of cervical motion was well preserved. CONCLUSION: Anterior odontoid screw fixation and posterior direct C2 percutaneous pedicle screw fixation with the aid of O-arm navigation and neurophysiological monitoring can be an interesting alternative option for complicated multiple axis fractures.

Recombinant human platelet-derived growth factor-BB versus autologous bone graft in foot and ankle fusion: A systematic review and meta-analysis.

Today, autogenous bone graft (ABG) is still considered as the gold standard for joint fusion. Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) which is of chemotactic and mitogenic to mesenchymal stem cells and possesses outstanding osteogenetic potentials has been used for ankle and foot fusion in recent years. The goal of this article is to evaluate the safety and efficacy of rhPDGF-BB versus ABG in foot and ankle fusion. The PubMed MEDLINE, EMBASE, Web of Science, and Cochrane Library were systematic searched. Finally, three randomized controlled trials (RCTs) with 634 patients were enrolled in this study. Results of radiologic effectiveness which included CT and radiographic union rates revealed that there was no significant difference between rhPDGF-BB approach and ABG approach. Analysis of clinical results held the same outcomes expect that ABG group was superior in long-term Short Form-12 physical component scores. The pooled results also demonstrated that rhPDGF-BB was as safe as ABG in foot and ankle surgery. However, autograft harvesting procedure has some drawbacks such as donor-site pain and morbidity, additional operation time, blood loss, and scarring, which can be overcome by rhPDGF-BB. Thus, rhPDGF-BB is a viable alternative to autograft in foot and ankle fusion surgery. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.

Can Unilateral Kyphoplasty Replace Bilateral Kyphoplasty in Treatment of Osteoporotic Vertebral Compression Fractures? A Systematic Review and Meta-analysis.

BACKGROUND: Kyphoplasty has been proven to be an efficient method to relieve patient suffering from osteoporotic vertebral compression fractures (OVCFs). Because of its technological superiority, unilateral kyphoplasty consumes less operative time and bone cement than traditional bilateral kyphoplasty. However, there is controversy about which method is most efficient in the treatment of OVCFs. Thus, an overall analysis should be performed to shed light on the facts corroborating both procedures. OBJECTIVE: To evaluate the safety and efficacy of unipedicular kyphoplasty versus bipedicular kyphoplasty in treating OVCFs. STUDY DESIGN: Inclusion criteria were randomized controlled trials focusing on comparing unilateral versus bilateral balloon kyphoplasty in treatment of OVCFs. The exclusion criteria contained infection, neoplastic etiology, traumatic fracture, neural compression, neurological deficit, spinal stenosis, previous surgery at the involved vertebral body, long-term use of steroids, and kyphoplasty with other invasive or semi-invasive intervention treatment. Retrospective studies, reviews, technology introductions, and biochemical trials were also excluded. SETTINGS: The PubMed MEDLINE, Cochrane Library, Web of Science, and EMBASE were systematic searched. Only randomized controlled trials published up to June 2015 comparing unilateral kyphoplasty with bilateral kyphoplasty in treatment of OVCFs were identified. METHODS: Two researchers independently screeded the works for inclusion and data extraction. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used to assess the methodological quality and evidence synthesis. RESULTS: Six articles with 563 patients were enrolled in this study. Results showed that the unilateral approach required less surgical time (MD, -23.19; 95% CI, [-27.08, -19.31]; P < 0.00001) and cement consumption (MD, -2.07; 95% CI, [-2.23, -1.91]; P < 0.00001), as well as a reduced cement leakage ratio (RR, 0.59; 95% CI, [0.35, 0.99]; P < 0.05) and improved short-term general health (MD, 1.48; 95% CI, [0.02, 2.93], P < 0.05). No significant difference was found in the visual analog scale score (short-term and long-term), Oswestry Disability Index score (mid-term and long-term) kyphotic angle reduction, restoration rate of anterior vertebral height, vertebral height loss rate, postoperative adjacent-level fractures, or in other assessments of 36-Item Short Form Health Survey parameters (short-term and long-term). LIMITATIONS: Only 6 studies were included, so that the sample size was still relatively small and publication bias could not be revealed in this study. Observation time of some data was inconsistent. All of these problems could influence the reliability of the results. CONCLUSION: Both unilateral kyphoplasty and bilateral kyphoplasty are safe and effective treatments for OVCFs. However, when operative time, cement volume, cement leakage, short-term general health, radiation dose, and hospitalization costs are taken into consideration, unilateral kyphoplasty may be the better choice. Yet, more high-quality RCTs with long-term follow-up are still required to make the final conclusion.Key words: Kyphoplasty, unilateral approach, bilateral approach, osteoporotic vertebral compression fractures, meta-analysis.

[Clinical effects of arthroscopic reconstruction of anterior cruciate ligament and minimally invasive reconstruction of posteromedial corner].

OBJECTIVE: To evaluate the clinical effects of arthroscopic reconstruction of anterior cruciate ligament (ACL) and minimally invasive reconstruction of posteromedial corner (PMC). METHODS: There were 22 cases of ACL and PMC tear were performed with reconstruction from March 2012 to February 2014. The patients were 29.4 years old on average, including 8 males and 14 females. ACL reconstruction was performed under arthroscopy and PMC reconstruction was performed minimally invasively through the ACL incision. The stability of knee was assessed by anterior drawer test,Lachman test,vulgus stress test and Slocum test. The function of knee was assessed by Lysholm score and Tegner activity rating. MRI of knee was checked 12 months after operation. RESULTS: The stability tests of all patients were negative at 2 and 6 months after operation, and there was one positive case in anterior drawer test and another positive case in vulgus stress test at 12 months after operation. Lysholm score of all patients 12 months after operation was 96.8 +/- 6.8, which was significantly better than 32.0 +/- 11.2 before operation. Tegner activity rating of all patients at 12 months postoperatively was 6.1 +/- 0.9, which was significantly better than 0.9 +/- 0.5 before operation. It showed the grafts were very well in the MRI 12 months postoperatively. CONCLUSION: Arthroscopic ACL reconstruction and minimally invasive PMC reconstruction can restore the stability of knee.

[Mechanisms involved in the effect of aerobic exercise on knee osteoarthritis].

With the aging of the population, the incidence of knee osteoarthritis (KOA) is increasing year by year. Exercise is one of the none medicine therapies in KOA rehabilitation. When making proper KOA exercise prescription, it's necessary to consider about the mechanisms involved in the interaction between exercise and articular cartilage, and obey the principle of choosing right programs, moderate frequency and intensity avoiding the injury of articular cartilage. The standard of KOA sport prescription is still controversial, so the mechanisms involved in the effect of aerobic exercise on protecting and damaging the articular cartilage need further research.

VdCYC8, Encoding CYC8 Glucose Repression Mediator Protein, Is Required for Microsclerotia Formation and Full Virulence in Verticillium dahliae.

Verticillium dahliae is the primary causal agent for Verticillium wilt disease on a diverse array of economically important crops, including cotton. In previous research, we obtained the low-pathogenicity mutant T286 from the T-DNA insertional mutant library of the highly virulent isolate Vd080 derived from cotton. In this study, the target disrupted gene VdCYC8 was identified by TAIL-PCR, encoding a homolog of CYC8 proteins involved in glucose repression. The deletion mutant ΔCYC8 exhibited several developmental deficiencies, including reduced microsclerotia formation, reduced sporulation, and slower growth. Moreover, compared with the wild type strain Vd080, the pathogenicity of strain ΔCYC8 was significantly decreased on cotton seedlings. However, the complementary mutants ΔCYC8-C led to restoration of the wild type phenotype or near wild type levels of virulence on cotton. Interestingly, pathogenicity of the strains was correlated with VdCYC8 gene expression levels in complemented mutants. Gene expression analyses in the wild type strain Vd080, the ΔCYC8-45 strain, and complemented strain ΔCYC8-C26 indicated that VdCYC8 regulates the transcription levels of several genes in V. dahliae that have roles in melanin and production.

Vibsanin B preferentially targets HSP90ß, inhibits interstitial leukocyte migration, and ameliorates experimental autoimmune encephalomyelitis.

Interstitial leukocyte migration plays a critical role in inflammation and offers a therapeutic target for treating inflammation-associated diseases such as multiple sclerosis. Identifying small molecules to inhibit undesired leukocyte migration provides promise for the treatment of these disorders. In this study, we identified vibsanin B, a novel macrocyclic diterpenoid isolated from Viburnum odoratissimum Ker-Gawl, that inhibited zebrafish interstitial leukocyte migration using a transgenic zebrafish line (TG:zlyz-enhanced GFP). We found that vibsanin B preferentially binds to heat shock protein (HSP)90ß. At the molecular level, inactivation of HSP90 can mimic vibsanin B's effect of inhibiting interstitial leukocyte migration. Furthermore, we demonstrated that vibsanin B ameliorates experimental autoimmune encephalomyelitis in mice with pathological manifestation of decreased leukocyte infiltration into their CNS. In summary, vibsanin B is a novel lead compound that preferentially targets HSP90ß and inhibits interstitial leukocyte migration, offering a promising drug lead for treating inflammation-associated diseases.

miR-142-3p acts as an essential modulator of neutrophil development in zebrafish.

Neutrophils play critical roles in vertebrate innate immune responses. As an emerging regulator in normal myelopoiesis, the precise roles of microRNA in the development of neutrophils have yet to be clarified. Using zinc-finger nucleases, we have successfully generated heritable mutations in miR-142a and miR-142b and showed that hematopoietic-specific miR-142-3p is completely deleted in miR-142 double mutant zebrafish. The lack of miR-142-3p resulted in aberrant reduction and hypermaturation of neutrophils in definitive myelopoiesis, as well as impaired inflammatory migration of neutrophils in the fetal stage. Furthermore, the adult myelopoiesis in the miR-142-3p-deficient zebrafish was also affected, producing irregular hypermature neutrophils with increased cell size and a decreased nucleocytoplasmic ratio. Additionally, miR-142-3p-deficient zebrafish are expected to develop a chronic failure of myelopoiesis with age. Transcriptome analysis showed an aberrant activation of the interferon γ (IFN-γ) signaling pathway in myelomonocytes after miR-142-3p deletion. We found that the reduced number and hypermaturation of neutrophils caused by loss of miR-142-3p was mainly mediated by the abnormally activated IFN-γ signaling, especially the upregulation of stat1a and irf1b. Taken together, we uncovered a novel role of miR-142-3p in maintaining normal neutrophil development and maturation.

[Effect of icariin on bone destruction and serum RANKL/OPG levels in type II collagen-induced arthritis rats].

OBJECTIVE: To observe the effect of Icariin (ICA) on serum receptor activator of NFkappaB-ligand (RANKL)/osteoprotegerin (OPG) production and bone destruction in type II collagen-induced arthritis (CIA) rats. METHODS: The CIA rat model was established in all rats, except those in the normal group (n = 8) using bovine type II collagen and complete Freund's adjuvant. Totally 24 CIA rats with arthritis index (AI) > or = 6 were selected and divided into the model group, the methotrexate (MTX) group, and the ICA group according to the AI score, 8 in each group. Normal saline was given to rats in the normal group and the model group by gastrogavage. MTX at the weekly dose of 5 mg/kg was given to rats in the MTX group. ICA at the daily dose of 20 mg/kg was given to rats in the ICA group. All medication lasted for 4 weeks. The AI scores were recorded once a week. Histomorphologic changes of the ankle joint were observed by HE staining. The bone destruction and the osteoporosis of the foot phalanx were detected by X-ray. Serum levels of RANKL and OPG were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: After 4-week intervention, when compared with the model group, AI score and Larsen score were significantly lower, the serum RANKL concentration and the RANKL/OPG ratio obviously decreased, while the serum OPG concentration obviously increased in the CIA group (P < 0.05, P < 0.01). In the MTX group, the aforesaid indices decreased, but without statistical difference (P > 0.05). Results of HE staining indicated that hyperplasia of joint synovium, infiltration of inflammatory cells, and the degree of articular cartilage destruction were obviously alleviated in the ICA group. CONCLUSION: ICA could alleviate or lessen the degree of articular cartilage destruction in CIA rats, and its mechanism might be associated with reducing serum levels of RANKL and elevating levels of OPG, thus further decreasing the ratio of RANKL/OPG.

Activated N-Ras signaling regulates arterial-venous specification in zebrafish.

BACKGROUND: The aberrant activation of Ras signaling is associated with human diseases including hematological malignancies and vascular disorders. So far the pathological roles of activated Ras signaling in hematopoiesis and vasculogenesis are largely unknown. METHODS: A conditional Cre/loxP transgenic strategy was used to mediate the specific expression of a constitutively active form of human N-Ras in zebrafish endothelial and hematopoietic cells driven by the zebrafish lmo2 promoter. The expression of hematopoietic and endothelial marker genes was analyzed both via whole mount in situ hybridization (WISH) assay and real-time quantitative PCR (qPCR). The embryonic vascular morphogenesis was characterized both by living imaging and immunofluorescence on the sections with a confocal microscopy, and the number of endothelial cells in the embryos was quantified by flow cytometry. The functional analyses of the blood circulation were carried out by fluorescence microangiography assay and morpholino injection. RESULTS: In the activated N-Ras transgenic embryos, the primitive hematopoiesis appeared normal, however, the definitive hematopoiesis of these embryos was completely absent. Further analysis of endothelial cell markers confirmed that transcription of arterial marker ephrinB2 was significantly decreased and expression of venous marker flt4 excessively increased, indicating the activated N-Ras signaling promotes the venous development at the expense of arteriogenesis during zebrafish embryogenesis. The activated N-Ras-expressing embryos showed atrophic axial arteries and expansive axial veins, leading to no definitive hematopoietic stem cell formation, the blood circulation failure and subsequently embryonic lethality. CONCLUSIONS: Our studies revealed for the first time that activated N-Ras signaling during the endothelial differentiation in vertebrates can disrupt the balance of arterial-venous specification, thus providing new insights into the pathogenesis of the congenital human vascular disease and tumorigenic angiogenesis.

Cannabinoid receptor 2 suppresses leukocyte inflammatory migration by modulating the JNK/c-Jun/Alox5 pathway.

BACKGROUND: The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. RESULTS: Cnr2 activation down-regulates 5-lipoxygenase (Alox5) expression by suppressing the JNK/c-Jun activation. CONCLUSION: The Cnr2-JNK-Alox5 axis modulates leukocyte inflammatory migration. SIGNIFICANCE: Linking two important regulators in leukocyte inflammatory migration and providing a potential therapeutic strategy for treating human inflammation-associated diseases. Inflammatory migration of immune cells is involved in many human diseases. Identification of molecular pathways and modulators controlling inflammatory migration could lead to therapeutic strategies for treating human inflammation-associated diseases. The role of cannabinoid receptor type 2 (Cnr2) in regulating immune function had been widely investigated, but the mechanism is not fully understood. Through a chemical genetic screen using a zebrafish model for leukocyte migration, we found that both an agonist of the Cnr2 and inhibitor of the 5-lipoxygenase (Alox5, encoded by alox5) inhibit leukocyte migration in response to acute injury. These agents have a similar effect on migration of human myeloid cells. Consistent with these results, we found that inactivation of Cnr2 by zinc finger nuclease-mediated mutagenesis enhances leukocyte migration, while inactivation of Alox5 blocks leukocyte migration. Further investigation indicates that there is a signaling link between Cnr2 and Alox5 and that alox5 is a target of c-Jun. Cnr2 activation down-regulates alox5 expression by suppressing the JNK/c-Jun activation. These studies demonstrate that Cnr2, JNK, and Alox5 constitute a pathway regulating leukocyte migration. The cooperative effect between the Cnr2 agonist and Alox5 inhibitor also provides a potential therapeutic strategy for treating human inflammation-associated diseases.