Photoresponsive metal-organic framework with combined photodynamic therapy and hypoxia-activated chemotherapy for the targeted treatment of rheumatoid arthritis.

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.

Evaluating the effectiveness and safety of acupuncture on serum uric acid in asymptomatic hyperuricemia population: a randomized controlled clinical trial study protocol.

Background: The clinical dangers of asymptomatic hyperuricemia to human health have become increasingly prominent over the past 20 years. Previous studies have shown the potential benefits of acupuncture on uric acid levels in the body. However, definitive evidence is lacking. Our objective is to evaluate the efficacy and safety of acupuncture on serum uric acid (SUA) in individuals with asymptomatic hyperuricemia. Methods: This is a randomized, single-blind, sham-controlled trial. A total of 180 eligible patients with asymptomatic hyperuricemia will be recruited at three hospitals in China. Patients will be randomly assigned in a 1:1 ratio to receive 16 sessions of manual acupuncture or sham acupuncture for 8 weeks. Patients will be followed up for 12 weeks. The primary outcome will be the change in SUA levels at week 8 after randomization. Secondary outcomes will include dynamic changes in SUA levels, efficacy rates, proportion of gout flare, body weight, and acute medication intake. The MGH Acupuncture Sensation Scale and adverse events related to acupuncture will be measured after each treatment. A blinding assessment will be performed on patients who receive at least one session of acupuncture. Data analyses will be performed on a full analysis set and a per-protocol set. Ethics and dissemination: Ethics approval has been obtained from the Clinical Trial Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology (approval no. 2021-S135). Written informed consent will be obtained from enrolled patients. The findings will be disseminated in a peer-reviewed journal. Clinical trial registration: ClinicalTrials.gov identifier, NCT05406830.

Cardiac-targeted delivery of nuclear receptor RORα via ultrasound targeted microbubble destruction optimizes the benefits of regular dose of melatonin on sepsis-induced cardiomyopathy.

BACKGROUND: Large-dose melatonin treatment in animal experiments was hardly translated into humans, which may explain the dilemma that the protective effects against myocardial injury in animal have been challenged by clinical trials. Ultrasound-targeted microbubble destruction (UTMD) has been considered a promising drug and gene delivery system to the target tissue. We aim to investigate whether cardiac gene delivery of melatonin receptor mediated by UTMD technology optimizes the efficacy of clinically equivalent dose of melatonin in sepsis-induced cardiomyopathy. METHODS: Melatonin and cardiac melatonin receptors in patients and rat models with lipopolysaccharide (LPS)- or cecal ligation and puncture (CLP)-induced sepsis were assessed. Rats received UTMD-mediated cardiac delivery of RORα/cationic microbubbles (CMBs) at 1, 3 and 5 days before CLP surgery. Echocardiography, histopathology and oxylipin metabolomics were assessed at 16-20 h after inducing fatal sepsis. RESULTS: We observed that patients with sepsis have lower serum melatonin than healthy controls, which was observed in the blood and hearts of Sprague-Dawley rat models with LPS- or CLP-induced sepsis. Notably, a mild dose (2.5 mg/kg) of intravenous melatonin did not substantially improve septic cardiomyopathy. We found decreased nuclear receptors RORα, not melatonin receptors MT1/2, under lethal sepsis that may weaken the potential benefits of a mild dose of melatonin treatment. In vivo, repeated UTMD-mediated cardiac delivery of RORα/CMBs exhibited favorable biosafety, efficiency and specificity, significantly strengthening the effects of a safe dose of melatonin on heart dysfunction and myocardial injury in septic rats. The cardiac delivery of RORα by UTMD technology and melatonin treatment improved mitochondrial dysfunction and oxylipin profiles, although there was no significant influence on systemic inflammation. CONCLUSIONS: These findings provide new insights to explain the suboptimal effect of melatonin use in clinic and potential solutions to overcome the challenges. UTMD technology may be a promisingly interdisciplinary pattern against sepsis-induced cardiomyopathy.

Research on the mechanisms of Shu Yu wan in the treatment of cervical cancer based on network pharmacology analyses and molecular docking technology.

Combining network pharmacology with molecular docking, our study revealed the candidate targets and mechanisms of Shu Yu Wan (SYW) for treating cervical cancer (CC). The targets associated with CC and active compounds in SYW were identified through TCGA, GeneCards and TCMSP databases. Consequently, a total of 16 active compounds in SYW and 38 common targets related to CC were predicted. Genes TP53 and CDK2 are among the hub genes in the PPI network. The results of GO and KEGG enrichment analyses suggested that SYW exerted pharmacological effects on CC by regulating cellular senescence, p53 signaling pathway, cell cycle, apoptosis, viral carcinogenesis and human papillomavirus infection (HPV) signaling pathway. Finally, molecular docking confirmed a strong binding affinity between the main active compounds of SYW with the core target proteins.

Efficacy and Prognosis of Hyperbaric Oxygen as Adjuvant Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-Analysis Study.

Background: Preclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE. Methods: A systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis. Results: A total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)]. Conclusion: In light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic. Protocol Registration: PROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

Assessing the quality of the soil around a shale gas development site in a subtropical karst region in southwest China.

The construction of shale gas facilities disturbs large areas of land and affects soil quality and function. In this study, we investigated the properties (including physical, chemical, and microbiological indicators) of soil at three different distances from a shale gas development site (<30 m, 30-50 m, and 50-100 m) in a karst area in 2017 and 2020. Our results showed that the soil water content; available carbon, nitrogen, and phosphorus concentrations; total nitrogen and total phosphorus concentrations; microbial biomass, and enzyme activities increased (P < 0.05) as the distance from the well pad increased, and the total carbon content, pH, electrical conductivity, and some ions (magnesium, sodium, and potassium) decreased with distance from the well pad (P < 0.05). The differences in the soil properties were most noticeable in 2017. The increases in the available nutrients were greater than in the total nutrients. The overall soil quality after the shale gas well pad construction was limited by the microbial biomass and sodium contents. The soil properties recovered most quickly at 30-50 m from the well pad, because of local farmland management practices that improved the soil properties and microbial biomass, and reduced the microbial stress. Therefore, we recommend planting sodium-tolerant crops on the land closest to the well pads, to facilitate restoration of the soil that was disturbed during the construction period.

Near-infrared triggered ropivacaine liposomal gel for adjustable and prolonged local anaesthesia.

Local analgesics effectively allow patients to relieve postoperative pain and reduce the need for inhaled general anesthetics or opioids. Compared with other similar long-acting local anesthetics, ropivacaine (Rop) is widely used due to its potential to minimize cardiotoxicity. However, the relatively short duration of Rop efficacy, which lasts for several hours after injection, is considered insufficient for long-term acute and chronic pain treatment. At present, repeated injections or indwelling catheters are used to achieve long-term drug delivery, which can easily cause infection and inflammation. To achieve externally controllable analgesia for a prolonged time, we prepared near-infrared (NIR)-responsive Rop liposomes (Rop@Lip) containing photosensitizers PdPC(OBu)8 and unsaturated phospholipid DLPC. The particle size of the Rop@Lip was 234.73 ± 5.21 nm, the PDI was 0.42 ± 0.02, and the drug encapsulation rate was 94.62 ± 1.1%. The release of Rop was highly NIR-dependent in vitro and in vivo. To ensure that the liposomes reside around the nerve for an extended period, we next designed an in situ gel with chitosan (CS) and ß-sodium glycerophosphate (ß-GP) to form a liposomal gel (Lip/Gel). This Lip/Gel composite drug delivery system could be retained in vivo for 10 d, reduce the side effects caused by drug overdose, and prolong the duration of efficacy. In summary, the NIR-responsive Rop composite drug delivery system generated in this paper can effectively solve the shortcomings of traditional local injections, reduce the toxicity and side effects of free Rop, and provide a basis for a light-responsive delivery system of analgesic drugs.

Manual acupuncture versus sham acupuncture and usual care for the prevention of primary dysmenorrhea (PD): study protocol for a randomized controlled trial.

BACKGROUND: Primary dysmenorrhea (PD) is a leading cause of dysmenorrhea among adolescent girls. Manual acupuncture may be considered as an effective treatment for PD, but high-quality evidence remains limited. This trial aims to evaluate the efficacy and safety of acupuncture for the prevention of PD as compared with sham acupuncture and usual care. METHODS/DESIGN: This is a three-arm, randomized, controlled clinical trial in which the patients, assessors, and statisticians will be blinded. A total of 300 acupuncture-naive patients who were diagnosed as PD will be randomly allocated to the verum acupuncture, sham acupuncture, or usual care groups in a 2:2:1 ratio. Patients in the verum acupuncture group will receive manual acupuncture at specific acupuncture points with penetrating needling, while those in the sham acupuncture group will receive non-penetrating needling at non-acupuncture points. They will be given five sessions over a menstrual cycle for 3 menstrual cycles. Patients in the usual care group will receive health education and informed to receive manual acupuncture for free after waiting for 7 menstrual cycles. The primary outcome will be the change from baseline in the Cox Menstrual Symptom Scale Score (CMSS). The secondary outcomes will be the changes in Massachusetts General Hospital Acupuncture Sensation Scale (MASS), visual analog scale (VAS), Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2), Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI- II), Acupuncture Expectancy Scale (AES), 60-item NEO Personality Inventory-Short Form (NEO-FFI), and acute medication intake. The adverse events will be recorded at every visit. The analyses will be performed base on a full analysis set (FAS) and a per-protocol set (PPS). DISCUSSION: This study may provide high-quality evidence regarding the efficacy and safety of manual acupuncture for PD. In addition, the results of this study will help to identify the efficacy of acupuncture due to the specific effects of acupuncture or placebo effects of acupuncture ritual. TRIAL REGISTRATION: Clinical Trials.gov NCT02783534 . Registered on 26 May 2016.

Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial.

OBJECTIVE: To assess the efficacy of manual acupuncture as prophylactic treatment for acupuncture naive patients with episodic migraine without aura. DESIGN: Multicentre, randomised, controlled clinical trial with blinded participants, outcome assessment, and statistician. SETTING: Seven hospitals in China, 5 June 2016 to 15 November 2018. PARTICIPANTS: 150 acupuncture naive patients with episodic migraine without aura. INTERVENTIONS: 20 sessions of manual acupuncture at true acupuncture points plus usual care, 20 sessions of non-penetrating sham acupuncture at heterosegmental non-acupuncture points plus usual care, or usual care alone over 8 weeks. MAIN OUTCOME MEASURES: Change in migraine days and migraine attacks per four weeks during weeks 1-20 after randomisation compared with baseline (four weeks before randomisation). RESULTS: Among 150 randomised patients (mean age 36.5 (SD 11.4) years; 123 (82%) women), 147 were included in the full analysis set. Compared with sham acupuncture, manual acupuncture resulted in a significantly greater reduction in migraine days at weeks 13 to 20 and a significantly greater reduction in migraine attacks at weeks 17 to 20. The reduction in mean number of migraine days was 3.5 (SD 2.5) for manual versus 2.4 (3.4) for sham (adjusted difference -1.4, 95% confidence interval -2.4 to -0.3; P=0.005) at weeks 13 to 16 and 3.9 (3.0) for manual versus 2.2 (3.2) for sham (adjusted difference -2.1, -2.9 to -1.2; P<0.001) at weeks 17 to 20. At weeks 17 to 20, the reduction in mean number of attacks was 2.3 (1.7) for manual versus 1.6 (2.5) for sham (adjusted difference -1.0, -1.5 to -0.5; P<0.001). No severe adverse events were reported. No significant difference was seen in the proportion of patients perceiving needle penetration between manual acupuncture and sham acupuncture (79% v 75%; P=0.891). CONCLUSIONS: Twenty sessions of manual acupuncture was superior to sham acupuncture and usual care for the prophylaxis of episodic migraine without aura. These results support the use of manual acupuncture in patients who are reluctant to use prophylactic drugs or when prophylactic drugs are ineffective, and it should be considered in future guidelines. TRIAL REGISTRATION: Clinicaltrials.gov NCT02765581.

Salvia miltiorrhiza Restrains Reactive Oxygen Species-Associated Pulmonary Fibrosis via Targeting Nrf2-Nox4 Redox Balance.

Pulmonary fibrosis (PF) is characterized by myofibroblast activation, which can be triggered by oxidative stress. In this study, we investigated the antifibrotic effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on PF and examined the underlying molecular mechanism. EASM suppressed myofibroblast activation with reduced extracellular matrix deposition in the lungs of mice subjected to bleomycin (BLM) challenge, demonstrating the inhibitory effects on PF. EASM positively alleviated oxidative stress by upregulating nuclear factor-erythroid 2-related factor 2 (Nrf2) and concomitantly downregulating NADPH oxidase 4 (Nox4) in the lungs of BLM-treated mice. This effect was also observed in an in vitro model of transforming growth factor beta 1 (TGF-ß1)-stimulated fibroblast activation. EASM reduced reactive oxygen species (ROS) generation in fibroblasts by stabilizing Nrf2 protein with promoting kelch-like ECH-associated protein 1 (Keap1) degradation. Nrf2 knockdown in the lungs of BLM-treated mice diminished the inhibitory effects of EASM on fibrosis, providing evidence in vivo to address the unique role of Nrf2. Additionally, EASM inhibited TGF-ß1/Smad3 signaling by downregulating protein kinase C delta (PKC-δ) and Smad3 phosphorylation (p-Smad3), which led to suppression of the TGF-ß1-induced fibrogenic response. These results indicate that EASM exhibits potent antifibrotic activity in vitro and in vivo, which might be associated with activation of Nrf2 pathway and inhibition of TGF-ß1/Smad3 pathway. Our findings support that EASM may act as an effective antifibrotic remedy for PF.

Giving waterbodies the treatment they need: A critical review of the application of constructed floating wetlands.

Water quality is declining worldwide and an increasing number of waterbodies lose their ecological function due to human population growth and climate change. Constructed floating wetlands (CFWs) are a promising ecological engineering tool for restoring waterbodies. The functionality of CFWs has been studied in-situ, in mesocosms and in the laboratory, but a systematic review of the success of in situ applications to improve ecosystem health is missing to date. This review summarises the pollutant dynamics in the presence of CFWs and quantifies removal efficiencies for major pollutants with a focus on in situ applications, including studies that have only been published in the Chinese scientific literature. We find that well designed CFWs successfully decrease pollutant concentrations and improve the health of the ecosystem, shown by lower algae biomass and more diverse fish, algae and invertebrate communities. However, simply extrapolating pollutant removal efficiencies from small-scale experiments will lead to overestimating the removal capacity of nitrogen, phosphorus and organic matter of in situ applications. We show that predicted climate change and eutrophication scenarios will likely increase the efficiency rate of CFWs, mainly due to increased growth and pollutant uptake rates at higher temperatures. However, an increase in rainfall intensity could lead to a lower efficiency of CFWs due to shorter hydraulic retention times and more pollutants being present in the particulate, not the dissolved form. Finally, we develop a framework that will assist water resource managers to design CFWs for specific management purposes. Our review clearly highlights the need of more detailed in situ studies, particularly in terms of understanding the short- and long-term ecosystem response to CFWs under different climate change scenarios.

Osthole protects against Ang II-induced endotheliocyte death by targeting NF-κB pathway and Keap-1/Nrf2 pathway.

Osthole, the main active constituents in traditional Chinese medicine fructus cnidii, has anti-inflammatory and anti-oxidant activities. Apoptosis of vascular endothelial cells is an important cause of cardiovascular disease. Inflammation and oxidative stress are two key factors in injury of endotheliocyte. In this study, we investigated the effect of osthole on Ang II-induced apoptosis of rat aortic endothelial cells (RAECs) and explored the underlying mechanisms. In the present study, the protective effects of osthole on RAECs induced by Ang II in vitro were tested. Additionally, molecular docking and molecular dynamics (MD) simulations were utilized to investigate the potential binding mode of osthole to NF-κB and Keap1. Our results showed osthole remarkably attenuates Ang II-induced apoptosis of RAECs via alleviating inflammation and oxidative stress. Molecular docking and MD simulations revealed the potential interaction of osthole bind to the P65 subunit of NF-κB and the Keap1 protein, an adaptor for the degradation of Nrf2. We further found that osthole decreased Ang II-induced inflammation and oxidative stress through respectively modulating NF-κB and Nrf2 pathways in RAECs. These studies provide evidence that osthole may represent a potential therapeutic agent for the treatment of vascular injury.

Integrated assessment of heavy metal pollution using transplanted mussels in eastern Guangdong, China.

Heavy metal contamination has been widely studied in coastal areas around the world. However, integrative studies of heavy metals pollution by monitoring and characterizing sediments, organisms, and biomarkers as well as their holistic interactions are rare. Here, we selected a developed coastal area in eastern Guangdong, China as the study field. Heavy metal analysis (both in sediment and mussel) and biomarker tests, including neutral red retention time test (NRRT) and micronuclei (MN) test, were employed in the current research. Anthropogenic activities influenced the heavy metal levels in sediments. Significant relationships (p < 0.05) were observed in the concentrations of Cd, Cu, and Zn between sediments and transplanted mussel, and significant relationships (p < 0.05) were also observed in between the concentrations of Cd, Cu, and Zn in sediments and the NRRT of mussel. The potential ecological risk index (RI) of sediments significantly correlated with NRRT (R = -0.991, p < 0.05). In Hao River, where the highest RI of sediments was found, the highest MN frequency and the lowest NRRT in mussels were detected simultaneously. The results indicated that the heavy metal pollution might cause subcellular toxic and genotoxic effects on mussels, especially for those from polluted areas (i.e., Hao River). The present study suggests that the transplanted green-lipped mussels are suitable for assessing heavy metal pollution, especially for Cd, Cu, and Zn.

Copper chloride dose-dependently alters spatial learning and memory, and glutamate levels, in the hippocampus of rats.

Copper is a trace element which exerts an important role in neuronal functions. Excessive Cu exposure is associated with central nervous system dysfunction, including memory loss. The present study examined the effects of CuCl2 exposure on the spatial learning and memory of rats, and on metabolites in the hippocampus. A total of 60 male Sprague­Dawley rats (10 rats/group) were intraperitoneally injected with various doses (0, 0.5, 1.0, 2.0, 4.0 and 6.0 mg/kg) of CuCl2 three times every other day for 6 days. Rats administered with 1.0 ml/kg sterile saline were used as controls. A total of 2 days subsequent to the final injection, the rats were subjected to the Morris water maze (MWM) test, followed by proton magnetic resonance spectroscopy (1H­MRS). The rats were subsequently sacrificed, and their hippocampal tissues were processed for high performance liquid chromatography (HPLC). The MWM test demonstrated that the high­dose groups exhibited worse spatial learning and memory compared with the controls; however, the rats that received a relatively low dose (2.0 mg/kg) exhibited a decreased impairment. The 1H­MRS results revealed increased Glu, N­acetyl­L­aspartate (NAA)+N­acetylaspartylglutamate, phosphocreatine (PCr) and Cr+PCr levels in the hippocampus of the 2.0 mg/kg group. HPLC analysis revealed increased γ­aminobutyric acid and glutamate (Glu) levels in the 2.0 mg/kg group, and decreased Glu levels in the 6.0 mg/kg group. The results of the present study demonstrated a beneficial effect of short­term exposure to a relatively low dose of CuCl2 on spatial learning and memory, and the association of this effect with increased NAA and Glu levels in the hippocampus.

T4-like phage Bp7, a potential antimicrobial agent for controlling drug-resistant Escherichia coli in chickens.

Chicken-pathogenic Escherichia coli is severely endangering the poultry industry in China and worldwide, and antibiotic therapy is facing an increasing problem of antibiotic resistance. Bacteriophages can kill bacteria with no known activity in human or animal cells, making them an attractive alternative to antibiotics. In this study, we present the characteristics of a novel virulent bacteriophage, Bp7, specifically infecting pathogenic multidrug-resistant E. coli. Phage Bp7 was isolated from chicken feces. Bp7 belongs to the family Myoviridae, possessing an elongated icosahedral head and contractile sheathed tail. It has a 168-kb double-stranded DNA genome. For larger yields, its optimal multiplicity of infection (MOI) to infect E. coli was about 0.001. The latent period was 10 to 15 min, and the burst size was 90 PFU/infected cell. It was stable both at pH 5.0 to 10.0 and at 40°C or 50°C for at least 1 h. Bp7 could infect 46% of pathogenic clinical E. coli strains. Bp7 harbored 791 open reading frames (ORFs) and 263 possible genes. Among the 263 genes, 199 possessed amino acid sequence identities with ORFs of phage T4, 62 had identities with other T4-like phages, and only one lacked any database match. The genome of Bp7 manifested obvious division and rearrangement compared to phages T4, JS98, and IME08. Bp7 is a new member of the "T4-like" genus, family Myoviridae. Its wide host range, strong cell-killing activity, and high stability to pH make it an alternative to antimicrobials for controlling drug-resistant E. coli in chickens.

Bifidobacterium longum as an oral delivery system of endostatin for gene therapy on solid liver cancer.

To overcome difficulties that hampered widespread application of a specific delivery system in cancer gene therapy and to inhibit the growth of solid liver cancer, we utilized a strain of Bifidobacterium longum as a delivery system to transport an endostatin gene that can inhibit growth of tumor. The B. longum strain with the endostatin gene (B. longum-En) was taken orally by tumor-bearing nude mice through drencher preparation. The results showed that B. longum-En could strongly inhibit the growth of solid liver tumor in nude mice and prolong the survival time of tumor-bearing nude mice. Furthermore, tumor growth was inhibited more efficiently when the B. longum-En treatment included selenium. Enriching the B. longum-En treatment with selenium improves the activity of NK and T cells and stimulates the activity of IL-2 and TNF-alpha in BALB/c mice. These results suggest that B. longum may be a highly specific and efficient vector for transporting anticancer genes in cancer gene therapy.

Critical role of vitamin D in sulfate homeostasis: regulation of the sodium-sulfate cotransporter by 1,25-dihydroxyvitamin D3.

As the fourth most abundant anion in the body, sulfate plays an essential role in numerous physiological processes. One key protein involved in transcellular transport of sulfate is the sodium-sulfate cotransporter NaSi-1, and previous studies suggest that vitamin D modulates sulfate homeostasis by regulating NaSi-1 expression. In the present study, we found that, in mice lacking the vitamin D receptor (VDR), NaSi-1 expression in the kidney was reduced by 72% but intestinal NaSi-1 levels remained unchanged. In connection with these findings, urinary sulfate excretion was increased by 42% whereas serum sulfate concentration was reduced by 50% in VDR knockout mice. Moreover, levels of hepatic glutathione and skeletal sulfated proteoglycans were also reduced by 18 and 45%, respectively, in the mutant mice. Similar results were observed in VDR knockout mice after their blood ionized calcium levels and rachitic bone phenotype were normalized by dietary means, indicating that vitamin D regulation of NaSi-1 expression and sulfate metabolism is independent of its role in calcium metabolism. Treatment of wild-type mice with 1,25-dihydroxyvitamin D3 or vitamin D analog markedly stimulated renal NaSi-1 mRNA expression. These data provide strong in vivo evidence that vitamin D plays a critical role in sulfate homeostasis. However, the observation that serum sulfate and skeletal proteoglycan levels in normocalcemic VDR knockout mice remained low in the absence of rickets and osteomalacia suggests that the contribution of sulfate deficiency to development of rickets and osteomalacia is minimal.

[The construction of cDNA expression library from the tentacles of Sagartia rosea].

A cDNA expression library of the tentacles of Sagartia rosea was constructed. The cDNA was cloned into eukaryotical expression plasmid pcDNA3. SMART protocol was used for cDNA library construction and bioinformatics analysis was carried out. 71 novel EST clones were obtained from 130 sequences in the library, of which there were 21 full-length clones, including cytolysin genes, flourescent protein, ubiquinol-cytochrome C reductase gene, elongation factor, ferritin gene riboflavin kinase gene, ribosomal protein. This provides a base for further investigating their biological activity and application.