Screening of Specific and Common Pathways in Breast Cancer Cell Lines MCF-7 and MDA-MB-231 Treated with Chlorophyllides Composites.

Our previous findings have shown that the chlorophyllides composites have anticancer activities to breast cancer cell lines (MCF-7 and MDA-MB-231). In the present study, microarray gene expression profiling was utilized to investigate the chlorophyllides anticancer mechanism on the breast cancer cells lines. Results showed that chlorophyllides composites induced upregulation of 43 and 56 differentially expressed genes (DEG) in MCF-7 and MDA-MB-231 cells, respectively. In both cell lines, chlorophyllides composites modulated the expression of annexin A4 (ANXA4), chemokine C-C motif receptor 1 (CCR1), stromal interaction molecule 2 (STIM2), ethanolamine kinase 1 (ETNK1) and member of RAS oncogene family (RAP2B). Further, the KEGG annotation revealed that chlorophyllides composites modulated DEGs that are associated with the endocrine system in MCF-7 cells and with the nervous system in MDA-MB-231 cells, respectively. The expression levels of 9 genes were validated by quantitative reverse transcription PCR (RT-qPCR). The expression of CCR1, STIM2, ETNK1, MAGl1 and TOP2A were upregulated in both chlorophyllides composites treated-MCF-7 and MDA-MB-231 cells. The different expression of NLRC5, SLC7A7 and PKN1 provided valuable information for future investigation and development of novel cancer therapy.

Improvement in the Blood Urea Nitrogen and Serum Creatinine Using New Cultivation of Cordyceps militaris.

Background: Chronic kidney disease (CKD) is a critical public health issue with a huge financial burden for both patients and society worldwide. Unfortunately, there are currently no efficacious therapies to prevent or delay the progression of end-stage renal disease (ESRD). Traditional Chinese medicine practices have shown that Cordyceps militaris (C. militaris) mycelia have a variety of pharmacologically useful properties, including antitumor, immunomodulation, and hepatoprotection. However, the effect of mycelial C. militaris on CKD remains unclear. Methods: Here, we investigated the effects of C. militaris mycelia on mice with CKD using four types of media: HKS, HKS with vitamin A (HKS + A), CM, and CM with vitamin A (CM + A). Results: The results at day 10 revealed that the levels of blood urea nitrogen (BUN) were significantly lower in the HKS (41%), HKS + A (41%), and CM + A (34%) groups compared with those in the corresponding control groups (nephrectomic mice). The level of serum creatinine in the HKS + A group decreased by 35% at day 10, whereas the levels in the HKS and CM + A groups decreased only by 14% and 13%, respectively, on day 30. Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effect on BUN, serum creatinine, body weight, total protein, and uric acid. Conclusions: Taken together, this is the first report using four new media (HKS, HKS + A, CM, and CM + A medium) for C. militaris mycelia. Each medium of mycelial C. militaris on CKD exhibits specific effects on BUN, serum creatinine, body weight, total protein, and uric acid. We concluded that treatment with C. militaris mycelia cultured in HKS or CM + A medium could potentially prevent the deterioration of kidney function in mice with CKD.

Chlorophyllides: Preparation, Purification, and Application.

Chlorophyllides can be found in photosynthetic organisms. Generally, chlorophyllides have a-, b-, c-, d-, and f-type derivatives, and all chlorophyllides have a tetrapyrrole structure with a Mg ion at the center and a fifth isocyclic pentanone. Chlorophyllide a can be synthesized from protochlorophyllide a, divinyl chlorophyllide a, or chlorophyll. In addition, chlorophyllide a can be transformed into chlorophyllide b, chlorophyllide d, or chlorophyllide f. Chlorophyllide c can be synthesized from protochlorophyllide a or divinyl protochlorophyllide a. Chlorophyllides have been extensively used in food, medicine, and pharmaceutical applications. Furthermore, chlorophyllides exhibit many biological activities, such as anti-growth, antimicrobial, antiviral, antipathogenic, and antiproliferative activity. The photosensitivity of chlorophyllides that is applied in mercury electrodes and sensors were discussed. This article is the first detailed review dedicated specifically to chlorophyllides. Thus, this review aims to describe the definition of chlorophyllides, biosynthetic routes of chlorophyllides, purification of chlorophyllides, and applications of chlorophyllides.

Facile production of chlorophyllides using recombinant CrCLH1 and their cytotoxicity towards multidrug resistant breast cancer cell lines.

The purity of chlorophylls plays one of the key role for the production of chlorophyllides. We have designed a facile method for chlorophyll purification by twice solvent extraction. Twice extraction causes the loss of chlorophylls, but the purity of total chlorophylls can be enhanced 182%. Then, the purified chlorophylls can be converted to relatively pure chlorophyllides facilely. The results show that higher purity of chlorophyllides could be obtained when purified chlorophylls (ethanol-hexane extract) was used as starting materials than that of crude chlorophylls (ethanol-only extract). In biocompatibility test, the results showed that the prepared chlorophyllides can be applied as biomaterials. When the prepared chlorophyllides were applied to anticancer tests, they were active both in MCF7 and MDA-MB-231 (multidrug resistant breast cancer cells) cell lines. In addition, the results suggested that the prepared chlorophyllides could be a potential candidate of combination therapy with doxorubicin to breast cancers.

Involvement of Aquaporins in the Intense Pulsed Light-Enhanced Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVES: We previously demonstrated that intense pulsed light (IPL) irradiation prior to wounding improved the wound healing in rats with diabetes mellitus (DM). Also, we found that IPL upregulated the expression of aquaporin 3 (AQP3), a protein that is crucial for wound healing, in normal rats. This present study aimed to examine the involvement of AQPs in the IPL-enhanced wound healing in diabetic rats. STUDY DESIGN/MATERIALS AND METHODS: Streptozotocin was used to induce diabetes in Sprague-Dawley rats. Animals were divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL irradiation and wounding (DM + IPL-Con group). Wounds were created on the dorsal skin of rats. The expressions of AQP1, 3, 4, 7, and 9 in the pre-injured skin, periwound, and wound were determined. RESULTS: Among all the AQPs analyzed, only the expressions of AQP3 and AQP7 were significantly altered. Unirradiated diabetic rats showed much higher expression level of AQP3 in the regenerating skin compared with normal rats. IPL pretreatment, but not concurrent treatment, attenuated the expression toward the level detected in the normal wounds. In contrast, a lower expression level of AQP7 was noted in the regenerating skin of DM only rats and IPL pretreatment upregulated the expression to a level similar to that in the normal rats. CONCLUSION: The beneficial effect of IPL pretreatment on the wound healing in diabetic rats might involve a mechanism by which the expression of AQPs is regulated. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Amino-Functionalized Nitrogen-Doped Graphene-Quantum-Dot-Based Nanomaterials with Nitrogen and Amino-Functionalized Group Content Dependence for Highly Efficient Two-Photon Bioimaging.

We fabricated nanomaterials comprising amino-functionalized and nitrogen-doped graphene quantum dots (amino-N-GQDs) and investigated their photostability and intrinsic luminescence in the near-infrared spectrum to determine their suitability as contrast agents in two-photon imaging (TPI). We observed that amino-N-GQDs with a higher amount of bonded nitrogen and amino-functionalized groups (6.2%) exhibited superior two-photon properties to those with a lower amount of such nitrogen and groups (4.9%). These materials were conjugated with polymers containing sulfur (polystyrene sulfonate, PSS) and nitrogen atoms (polyethylenimine, PEI), forming amino-N-GQD-PSS-PEI specimens (amino-N-GQD-polymers). The polymers exhibited a high quantum yield, remarkable stability, and notable two-photon properties and generated no reactive oxygen species, rendering them excellent two-photon contrast agents for bioimaging. An antiepidermal growth factor receptor (AbEGFR) was used for labeling to increase specificity. Two-photon imaging (TPI) of amino-N-GQD (6.2%)-polymer-AbEGFR-treated A431 cancer cells revealed remarkable brightness, intensity, and signal-to-noise ratios for each observation at a two-photon excitation power of 16.9 nJ pixel-1 under 30 scans and a three-dimensional (3D) depth of 105 µm, indicating that amino-N-GQD (6.2%)-polymer-AbEGFR-treated cells can achieve two-photon luminescence with 71 times less power required for two-photon autofluorescence (1322.8 nJ pixel-1 with 500 scans) of similar intensity. This economy can minimize photodamage to cells, rendering amino-N-GQD-polymers suitable for noninvasive 3D bioimaging.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

BACKGROUND AND OBJECTIVE: Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. MATERIALS AND METHODS: Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. RESULTS: There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. CONCLUSION: Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

Cytotoxic Effects of Chlorophyllides in Ethanol Crude Extracts from Plant Leaves.

Chlorophyllide (chlide) is a natural catabolic product of chlorophyll (Chl), produced through the activity of chlorophyllase (chlase). The growth inhibitory and antioxidant effects of chlide from different plant leaf extracts have not been reported. The aim of this study is to demonstrate that chlide in crude extracts from leaves has the potential to exert cytotoxic effects on cancer cell lines. The potential inhibitory and antioxidant effects of chlide in crude extracts from 10 plant leaves on breast cancer cells (MCF7 and MDA-MB-231), hepatocellular carcinoma cells (Hep G2), colorectal adenocarcinoma cells (Caco2), and glioblastoma cells (U-118 MG) were studied using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays. The results of the MTT assay showed that chlide in crude extracts from sweet potato were the most effective against all cancer cell lines tested. U-118 MG cells were the most sensitive, while Caco2 cells were the most resistant to the tested crude extracts. The cytotoxic effects of chlide and Chl in crude extracts from sweet potato and of commercial chlorophyllin (Cu-chlin), in descending order, were as follows: chlide > Chl > Cu-chlin. Notably, the IC50 of sweet potato in U-118 MG cells was 45.65 µg/mL while those of Chl and Cu-chlin exceeded 200 µg/mL. In the DPPH assay, low concentrations (100 µg/mL) of chlide and Cu-chlin from crude extracts of sweet potato presented very similar radical scavenging activity to vitamin B2. The concentration of chlide was negatively correlated with DPPH activity. The current study was the first to demonstrate that chlide in crude extracts from leaves have potential cytotoxicity in cancer cell lines. Synergism between chlide and other compounds from leaf crude extracts may contribute to its cytotoxicity.

Microfluidic Synthesis of Vinblastine-Loaded Multifunctional Particles for Magnetically Responsive Controlled Drug Release.

Vinblastine (VBL) is a major chemotherapeutic drug; however, in some cases, it may cause severe side effects in patients with cancer. Designing a novel VBL pharmaceutical formulation is a crucial and emerging concern among researchers for reducing the use of VBL. This study developed a stimuli-responsive controlled VBL drug release system from magnetically sensitive chitosan capsules. A magnetically responsive controlled drug release system was designed by embedding superparamagnetic iron oxide (SPIO) nanoparticles (NPs) in a chitosan matrix and an external magnet. In addition, droplet microfluidics, which is a novel technique for producing polymer spheres, was used for manufacturing monodispersed chitosan microparticles. The prepared VBL and SPIO NPs-loaded chitosan microparticles were characterized and analyzed using Fourier transform infrared spectroscopy, transmission electron microscopy, scanning electron microscopy, a superconducting quantum interference device, and a biocompatibility test. The drug encapsulation efficiency was 67%-69%. The in vitro drug release test indicated that the VBL could be 100% released from chitosan composite particles in 80-130 min under magnetic stimulation. The pulsatile magnetically triggered tests showed individual and distinctive controlled release patterns. Thus, the timing and dose of VBL release was controllable by an external magnet. The results presume that using a magnetically responsive controlled drug release system offers a valuable opportunity for VBL drug delivery, where the delivery system is an active participant, rather than a passive vehicle, in the optimization of cancer treatment. The proposed actively targeted magnetic drug delivery system offers many advantages over conventional drug delivery systems by improving the precision and timing of drug release, easy operation, and higher compliance for pharmaceutical applications.

Differences in Clinical Manifestations, Antimicrobial Susceptibility Patterns, and Mutations of Fluoroquinolone Target Genes between Chryseobacterium gleum and Chryseobacterium indologenes.

Chryseobacterium infections are uncommon, and previous studies have revealed that Chryseobacterium gleum is frequently misidentified as Chryseobacterium indologenes We aimed to explore the differences in clinical manifestations and antimicrobial susceptibility patterns between C. gleum and C. indologenes The database of a clinical microbiology laboratory was searched to identify patients with Chryseobacterium infections between 2005 and 2017. Species were reidentified using 16S rRNA gene sequencing, and patients with C. gleum and C. indologenes infections were included in the study. A total of 42 C. gleum and 84 C. indologenes isolates were collected from consecutive patients. A significant increase in C. indologenes incidence was observed. C. gleum was significantly more associated with bacteremia than C. indologenes Patients with C. gleum infections had more comorbidities of malignancy and liver cirrhosis than those with C. indologenes infections. The overall case fatality rate was 19.8%. Independent risk factors for mortality were female sex and C. indologenes infection. These isolates were most susceptible to minocycline (73%), followed by trimethoprim-sulfamethoxazole (47.6%), tigecycline (34.1%), and levofloxacin (32.5%). C. gleum exhibited a significantly higher rate of susceptibility than C. indologenes to piperacillin, piperacillin-tazobactam, ceftazidime, tigecycline, and levofloxacin. Alterations in DNA gyrase subunit A were identified to be associated with fluoroquinolone resistance in C. indologenes No nonsynonymous substitutions were observed in the quinolone resistance-determining regions (QRDRs) of C. gleum Differences in epidemiology, clinical manifestations, and antimicrobial susceptibility patterns exist between C. gleum and C. indologenes Additional investigations are needed to explore the significance of these differences.

Origination and selection of ABCDE and AGL6 subfamily MADS-box genes in gymnosperms and angiosperms

BACKGROUND: The morphological diversity of flower organs is closely related to functional divergence within the MADS-box gene family. Bryophytes and seedless vascular plants have MADS-box genes but do not have ABCDE or AGAMOUS-LIKE6 (AGL6) genes. ABCDE and AGL6 genes belong to the subgroup of MADS-box genes. Previous works suggest that the B gene was the first ABCDE and AGL6 genes to emerge in plant but there are no mentions about the probable origin time of ACDE and AGL6 genes. Here, we collected ABCDE and AGL6 gene 381 protein sequences and 361 coding sequences from gymnosperms and angiosperms and reconstructed a complete Bayesian phylogeny of these genes. In this study, we want to clarify the probable origin time of ABCDE and AGL6 genes is a great help for understanding the role of the formation of the flower, which can decipher the forming order of MADS-box genes in the future. RESULTS: These genes appeared to have been under purifying selection and their evolutionary rates are not significantly different from each other. Using the Bayesian evolutionary analysis by sampling trees (BEAST) tool, we estimated that: the mutation rate of the ABCDE and AGL6 genes was 2.617 × 10-3 substitutions/site/million years, and that B genes originated 339 million years ago (MYA), CD genes originated 322 MYA, and A genes shared the most recent common ancestor with E/AGL6 296 MYA, respectively. CONCLUSIONS: The phylogeny of ABCDE and AGL6 genes subfamilies differed. The APETALA1 (AP1 or A gene) subfamily clustered into one group. The APETALA3/PISTILLATA (AP3/PI or B genes) subfamily clustered into two groups: the AP3 and PI clades. The AGAMOUS/SHATTERPROOF/SEEDSTICK (AG/SHP/STK or CD genes) subfamily clustered into a single group. The SEPALLATA (SEP or E gene) subfamily in angiosperms clustered into two groups: the SEP1/2/4 and SEP3 clades. The AGL6 subfamily clustered into a single group. Moreover, ABCDE and AGL6 genes appeared in the following order: AP3/PI → AG/SHP/STK → AGL6/SEP/AP1. In this study, we collected candidate sequences from gymnosperms and angiosperms. This study highlights important events in the evolutionary history of the ABCDE and AGL6 gene families and clarifies their evolutionary path.

The Development of Peptide-based Antimicrobial Agents against Dengue Virus.

Dengue fever has become an imminent threat to international public health because of global warming and climate change. The World Health Organization proclaimed that more than 50% of the world's population is at risk of dengue virus (DENV) infection. Therefore, developing a clinically approved vaccine and effective therapeutic remedy for treating dengue fever is imperative. Peptide drug development has become a novel pharmaceutical research field. This article reviews various peptidesbased antimicrobial agents targeting three pathways involved in the DENV lifecycle. Specifically, they are peptide vaccines from immunomodulation, peptide drugs that inhibit virus entry, and peptide drugs that interfere with viral replication. Many antiviral peptide studies against DENV have been conducted in animal model trials, and progression to clinical trials for these promising peptide drugs is anticipated.

Complete Genome Sequence of Elizabethkingia miricola Strain EM798-26 Isolated from the Blood of a Cancer Patient.

Elizabethkingia miricola EM798-26 was isolated from the blood of a patient with diffuse large B-cell lymphoma in Taiwan. We report here the complete genome sequence of EM798-26, which contains a G+C content of 35.7% and 3,877 candidate protein-coding genes.

Genomic features, phylogenetic relationships, and comparative genomics of Elizabethkingia anophelis strain EM361-97 isolated in Taiwan.

Elizabethkingia anophelis has become an emerging infection in humans. Recent research has shown that previous reports of E. meningoseptica infections might in fact be caused by E. anophelis. We aimed to investigate the genomic features, phylogenetic relationships, and comparative genomics of this emerging pathogen. Elizabethkingia anophelis strain EM361-97 was isolated from the blood of a cancer patient in Taiwan. The total length of the draft genome was 4,084,052 bp. The whole-genome analysis identified the presence of a number of antibiotic resistance genes, which corresponded with the antibiotic susceptibility phenotype of this strain. Based on the average nucleotide identity, the phylogenetic analysis revealed that E. anophelis EM361-97 was a sister group to E. anophelis FMS-007, which was isolated from a patient with T-cell non-Hodgkin's lymphoma in China. Knowledge of the genomic characteristics and comparative genomics of E. anophelis will provide researchers and clinicians with important information to understand this emerging microorganism.

Risk of infection following colonoscopy and sigmoidoscopy in symptomatic patients.

Background and study aims Previous studies describing the incidence of infection after colonoscopy and sigmoidoscopy are limited. The aim of this study was to determine the incidence of infection, and to propose a nomogram to predict the probability of infection following colonoscopy and sigmoidoscopy in symptomatic patients. Patients and methods A nationwide retrospective study was conducted by analyzing the National Health Insurance Research Database of Taiwan. The incidence of infection within 30 days after colonoscopy and sigmoidoscopy was assessed and compared with a control group matched at a ratio of 1:1 based on age, sex, and the date of examination. Results In all, 112 543 patients who underwent colonoscopy or sigmoidoscopy and 112 543 matched patients who did not undergo these procedures were included. The overall incidence of infection within 30 days after colonoscopy and sigmoidoscopy was 0.37 %, which was significantly higher than that of the control group (0.04 %; P < 0.001). Diverticulitis, peritonitis, and appendicitis were the most common infections. Patients who underwent colonoscopy or sigmoidoscopy had a 9.38-fold risk of infection (95 % confidence interval, 6.81 - 12.93; P < 0.001) compared with the control group. The predicted infection-free rates of the nomogram were closely aligned with the actual infection-free rates, with a bootstrapping concordance index of 0.763. Conclusions Colonoscopy and sigmoidoscopy are associated with an increased risk of infection, which may occur after these procedures. Our nomogram may provide clinicians with an easy tool to evaluate the risk of infection after colonoscopy and sigmoidoscopy in symptomatic patients.

Analysis of Patients with Myelopathy due to Benign Intradural Spinal Tumors with Concomitant Lumbar Degenerative Diseases Misdiagnosed and Erroneously Treated with Lumbar Surgery.

OBJECTIVE: When a cervical or thoracic benign intradural spinal tumor (BIST) coexists with lumbar degenerative diseases (LDD), diagnosis can be difficult. Symptoms of BIST-myelopathy can be mistaken as being related to LDD. Worse, an unnecessary lumbar surgery could be performed. This study was conducted to analyze cases in which an erroneous lumbar surgery was undertaken in the wake of failure to identify BIST-associated myelopathy. METHODS: Cases were found in a hospital database. Patients who underwent surgery for LDD first and then another surgery for BIST removal within a short interval were studied. Issues investigated included why the BISTs were missed, how they were found later, and how the patients reacted to the unnecessary lumbar procedures. RESULTS: Over 10 years, 167 patients received both surgeries for LDD and a cervical or thoracic BIST. In 7 patients, lumbar surgery preceded tumor removal by a short interval. Mistakes shared by the physicians included failure to detect myelopathy and a BIST, and a hasty decision for lumbar surgery, which soon turned out to be futile. Although the BISTs were subsequently found and removed, 5 patients believed that the lumbar surgery was unnecessary, with 4 patients expressing regrets and 1 patient threatening to take legal action against the initial surgeon. CONCLUSIONS: Concomitant symptomatic LDD and BIST-associated myelopathy pose a diagnostic challenge. Spine specialists should refrain from reflexively linking leg symptoms and impaired ability to walk to LDD. Comprehensive patient evaluation is fundamental to avoid misdiagnosis and wrong lumbar surgery.

Risk of osteoporosis and pathologic fractures in cancer patients who underwent hematopoietic stem cell transplantation: a nationwide retrospective cohort study.

BACKGROUND: Long-term data on post-hematopoietic stem cell transplantation (HSCT) osteoporosis and fracture are limited. This study evaluated the long-term risk of osteoporosis and fracture in cancer patients who underwent HSCT. RESULTS: The incidence density rate of osteoporosis was 12.5 per 1000 person-years in the HSCT group, which was significantly higher than that in the non-HSCT group (5.65 per 1000 person-years) after adjustment for associated factors and consideration of competing risk factors (adjusted subhazard ratio, 1.48; 95% confidence interval, 1.06-2.07). The incidence density rate of fracture was 4.89 per 1000 person-years in the HSCT group, and the risk of fracture was 1.40 times higher in the HSCT group than in the non-HSCT group (95% confidence interval, 0.83-2.40). The vertebra was the most common site of fracture after HSCT (68.4%). The risk of osteoporosis and fracture significantly increased in post-HSCT patients with both hematological malignancies and solid tumors. Both autologous and allogeneic HSCTs increased the risk of osteoporosis, whereas only autologous HSCT recipients had an increased risk of fracture. MATERIALS AND METHODS: This nationwide retrospective cohort study analyzed data from Taiwan's National Health Insurance Research Database. We identified an HSCT group comprising 1040 cancer patients who underwent HSCT during 2000-2008 and a non-HSCT group comprising 4160 propensity score-matched cancer patients who did not undergo HSCT. All patients were followed up until the occurrence of osteoporosis; fracture; December 31, 2011; or withdrawal from the insurance program. CONCLUSIONS: HSCT recipients have an increased risk of osteoporosis.

Draft Genome Sequence of Elizabethkingia anophelis Strain EM361-97 Isolated from the Blood of a Cancer Patient.

Elizabethkingia anophelis EM361-97 was isolated from the blood of a patient with nasopharyngeal carcinoma and lung cancer. We report the draft genome sequence of EM361-97, which contains a G+C content of 35.7% and 3,611 candidate protein-encoding genes.

Risk of leukaemia in children infected with enterovirus: a nationwide, retrospective, population-based, Taiwanese-registry, cohort study.

BACKGROUND: The association between enterovirus infections in children and risk of leukaemia is unclear. We aimed to assess the risk of leukaemia after enterovirus infection in children. METHODS: We did a nationwide retrospective cohort study by analysing data from the National Health Insurance Research Database (NHIRD) in Taiwan. Children with enterovirus infections aged younger than 18 years were identified. With use of computer-generated random numbers, children not infected with enterovirus were randomly selected and frequency matched (1:1) with children infected with enterovirus by sex, age, urbanisation level, parental occupation, and index year of enterovirus infection. We only included children with complete baseline data for age and sex and who had at least three clinic visits with the diagnosis of enterovirus infection. The diagnosis date of the first clinic visit for the enterovirus infection was defined as the index date for initiation of follow-up person-year measurement and participants. All study patients were followed up until they developed leukaemia, were lost to follow-up, withdrew from the NHI programme, or until the end of the study without leukaemia (censored). Our primary endpoint was a diagnosis of leukaemia during follow-up. FINDINGS: Insurance claims data for 3 054 336 children younger than 18 years were randomly selected from all insured children in the NHIRD. We identified 282 360 children infected with enterovirus and 282 355 children not infected with enterovirus between Jan 1, 2000, and Dec 31, 2007. The incidence density rates of leukaemia were 3·26 per 100 000 person-years for the enterovirus-infected and 5·84 per 100 000 person-years for the non-enterovirus-infected cohorts. The risk of leukaemia was significantly lower in the enterovirus-infected cohort than in the non-enterovirus-infected cohort (adjusted subhazard ratio [SHR] 0·44, 95% CI 0·31-0·60; p<0·0001). Children infected with enterovirus have a reduced risk of both lymphocytic leukaemia (adjusted SHR 0·44, 0·30-0·65; p<0·0001) and acute myeloid leukaemia (adjusted SHR 0·40, 0·17-0·97; p=0·04). Herpangina and hand-foot-and-mouth disease were the main diseases associated with the reduced risk of leukaemia. INTERPRETATION: The association between enterovirus infection and the reduced risk of developing leukaemia supports Greaves' delayed infection hypothesis for the cause of childhood leukaemia.

Exendin-4-loaded PLGA microspheres relieve cerebral ischemia/reperfusion injury and neurologic deficits through long-lasting bioactivity-mediated phosphorylated Akt/eNOS signaling in rats.

Glucagon-like peptide-1 (GLP-1) receptor activation in the brain provides neuroprotection. Exendin-4 (Ex-4), a GLP-1 analog, has seen limited clinical usage because of its short half-life. We developed long-lasting Ex-4-loaded poly(D,L-lactide-co-glycolide) microspheres (PEx-4) and explored its neuroprotective potential against cerebral ischemia in diabetic rats. Compared with Ex-4, PEx-4 in the gradually degraded microspheres sustained higher Ex-4 levels in the plasma and cerebrospinal fluid for at least 2 weeks and improved diabetes-induced glycemia after a single subcutaneous administration (20 µg/day). Ten minutes of bilateral carotid artery occlusion (CAO) combined with hemorrhage-induced hypotension (around 30 mm Hg) significantly decreased cerebral blood flow and microcirculation in male Wistar rats subjected to streptozotocin-induced diabetes. CAO increased cortical O2(-) levels by chemiluminescence amplification and prefrontal cortex edema by T2-weighted magnetic resonance imaging analysis. CAO significantly increased aquaporin 4 and glial fibrillary acidic protein expression and led to cognition deficits. CAO downregulated phosphorylated Akt/endothelial nitric oxide synthase (p-Akt/p-eNOS) signaling and enhanced nuclear factor (NF)-κBp65/intercellular adhesion molecule-1 (ICAM-1) expression, endoplasmic reticulum (ER) stress, and apoptosis in the cerebral cortex. PEx-4 was more effective than Ex-4 to improve CAO-induced oxidative injury and cognitive deficits. The neuroprotection provided by PEx-4 was through p-Akt/p-eNOS pathways, which suppressed CAO-enhanced NF-κB/ICAM-1 signaling, ER stress, and apoptosis.