Cerebral Hemodynamic Responses to Acupuncture in Migraine Patients: A Systematic Review

ABSTRACTWe review the literature conjoining acupuncture, migraine, and cerebral hemodynamics. To do so, we searched PubMed in March 2013 for studies investigating cerebral hemodynamics with functional magnetic resonance imaging (fMRI), near-infrared spectroscopy (NIRS), transcranial Doppler (TCD) ultrasound, and other tools in migraineurs, acupuncture recipients, and migraineurs receiving acupuncture. Our search identified 1321 distinct articles – acupuncture (n=463), migraine (n=866), and both (n=8). Only three (n=3) satisfied our inclusion criteria. Based on these three, we found the following: (1) Acupuncture may positively influence not just dynamic, but also static cerebral autoregulation during the interictal phase, depending on the intervals between sessions of acupuncture as dose units. (2) TCD can detect pretreatment differences between responders and non-responders to acupuncture, which may be predictive of clinical response. (3) “Point-through-point” needling (at angles connecting acupoints) may be clinically superior to standard acupuncture, thus needling angles may affect treatment effectiveness. None of the reviewed articles investigated patient responses during migraine attack. Although the 2009 Cochrane review affirmed acupuncture as effective prophylaxis for migraine, few studies investigated the cerebrovascular aspects – only analyzing arterial blood flow, but not microcirculation. Future research is warranted in monitoring brain tissue oxygenation to investigate acupuncture as both a preventive and abortive treatment for migraine, varying the type and dose interval and analyzing variations in clinical response

The structural basis of actinomycin D–bindinginduces nucleotide flipping out, a sharp bendand a left-handed twist in CGG triplet repeats

The potent anticancer drug actinomycin D (ActD)functions by intercalating into DNA at GpC sites,thereby interrupting essential biological processesincluding replication and transcription. Certainneurological diseases are correlated with the expansionof (CGG)n trinucleotide sequences, whichcontain many contiguous GpC sites separated by asingle G:G mispair. To characterize the binding ofActD to CGG triplet repeat sequences, the structuralbasis for the strong binding of ActD to neighbouringGpC sites flanking a G:G mismatch has beendetermined based on the crystal structure of ActDbound to ATGCGGCAT, which contains a CGGtriplet sequence. The binding of ActD molecules toGCGGC causes many unexpected conformationalchanges including nucleotide flipping out, a sharpbend and a left-handed twist in the DNA helix via atwo site-binding model. Heat denaturation, circulardichroism and surface plasmon resonance analysesshowed that adjacent GpC sequences flanking aG:G mismatch are preferred ActD-binding sites. Inaddition, ActD was shown to bind the hairpin conformationof (CGG)16 in a pairwise combination andwith greater stability than that of other DNAintercalators. Our results provide evidence of apossible biological consequence of ActD bindingto CGG triplet repeat sequences

Self-Titrating Anticoagulant Nanocomplexes That Restore Homeostatic Regulation of the Coagulation Cascade

Antithrombotic therapy is a critical portion of the treatment regime for a number of life-threatening conditions, including cardiovascular disease, stroke, and cancer; yet, proper clinical management of anticoagulation remains a challenge because existing agents increase the propensity for bleeding in patients. Here, we describe the development of a bioresponsive peptide–polysaccharide nanocomplex that utilizes a negative feedback mechanism to self-titrate the release of anticoagulant in response to varying levels of coagulation activity. This nanoscale self-titrating activatable therapeutic, or nanoSTAT, consists of a cationic thrombin-cleavable peptide and heparin, an anionic polysaccharide and widely used clinical anticoagulant. Under nonthrombotic conditions, nanoSTATs circulate inactively, neither releasing anticoagulant nor significantly prolonging bleeding time. However, in response to life-threatening pulmonary embolism, nanoSTATs locally release their drug payload and prevent thrombosis. This autonomous negative feedback regulator may improve antithrombotic therapy by increasing the therapeutic window and decreasing the bleeding risk of anticoagulants.National Institutes of Health (U.S.) (R01CA124427-01)National Cancer Institute (U.S.) (U54CA119349)National Cancer Institute (U.S.) (U54CA119335)National Cancer Institute (U.S.) (Center of Cancer Nanotechnology Excellence at MIT-Harvard U54CA151884)David & Lucile Packard Foundation (Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Marie D. and Pierre Casimir-Lambert Fund)National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)MIT-Harvard Center of Cancer Nanotechnology Excellence (5 U54 CA151884-03)National Institutes of Health (U.S.). Medical Scientist Training Program (T32GM007753)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32CA159496-02)Burroughs Wellcome Fund (Career Award at the Scientific Interface

High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.

Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis

Cell-based analysis of Chikungunya virus E1 protein in membrane fusion

<p>Abstract</p> <p>Background</p> <p>Chikungunya fever is a pandemic disease caused by the mosquito-borne Chikungunya virus (CHIKV). E1 glycoprotein mediation of viral membrane fusion during CHIKV infection is a crucial step in the release of viral genome into the host cytoplasm for replication. How the E1 structure determines membrane fusion and whether other CHIKV structural proteins participate in E1 fusion activity remain largely unexplored.</p> <p>Methods</p> <p>A bicistronic baculovirus expression system to produce recombinant baculoviruses for cell-based assay was used. Sf21 insect cells infected by recombinant baculoviruses bearing wild type or single-amino-acid substitution of CHIKV E1 and EGFP (enhanced green fluorescence protein) were employed to investigate the roles of four E1 amino acid residues (G91, V178, A226, and H230) in membrane fusion activity.</p> <p>Results</p> <p>Western blot analysis revealed that the E1 expression level and surface features in wild type and mutant substituted cells were similar. However, cell fusion assay found that those cells infected by CHIKV E1-H230A mutant baculovirus showed little fusion activity, and those bearing CHIKV E1-G91D mutant completely lost the ability to induce cell-cell fusion. Cells infected by recombinant baculoviruses of CHIKV E1-A226V and E1-V178A mutants exhibited the same membrane fusion capability as wild type. Although the E1 expression level of cells bearing monomeric-E1-based constructs (expressing E1 only) was greater than that of cells bearing 26S-based constructs (expressing all structural proteins), the sizes of syncytial cells induced by infection of baculoviruses containing 26S-based constructs were larger than those from infections having monomeric-E1 constructs, suggesting that other viral structure proteins participate or regulate E1 fusion activity. Furthermore, membrane fusion in cells infected by baculovirus bearing the A226V mutation constructs exhibited increased cholesterol-dependences and lower pH thresholds. Cells bearing the V178A mutation exhibited a slight decrease in cholesterol-dependence and a higher-pH threshold for fusion.</p> <p>Conclusions</p> <p>Cells expressing amino acid substitutions of conserved protein E1 residues of E1-G91 and E1-H230 lost most of the CHIKV E1-mediated membrane fusion activity. Cells expressing mutations of less-conserved amino acids, E1-V178A and E1-A226V, retained membrane fusion activity to levels similar to those expressing wild type E1, but their fusion properties of pH threshold and cholesterol dependence were slightly altered.</p

Associations between child maltreatment and adolescents’ health-related quality of life and emotional and social problems in low-income families, and the moderating role of social support

This study aimed to examine the associations between different types of child maltreatment and health-related quality of life (HRQoL) and emotional and social problems in adolescents, and to examine the moderating effect of social support on those associations. A cross-sectional survey was conducted between January and June 2016 in Hong Kong. The sample comprised 351 parent and adolescent dyads from low-income families. The parents reported on child maltreatment (physical abuse, psychological aggression, and neglect), and the adolescents reported on their HRQoL, emotional problems, and social problems. The adolescents’ perceived social support was included as a potential moderator. Results of the study show that child physical abuse was strongly associated with emotional and social problems (B = 0.91-1.45, p &lt; .05). Lower overall HRQoL was associated with psychological aggression (B = −3.96, p &lt; .05) and neglect (B = −4.14, p &lt; .05). Physical functioning was affected by psychological aggression (B = −3.16, p &lt; .05), and emotional functioning was affected by neglect (B = −4.82, p &lt; .05). Social functioning was impacted by all three types of maltreatment (B = −9.16 to −5.26, p &lt; .05). This study extends previous literature by showing the varying effects of different types of child maltreatment on children’s health in the context of low-income families. The findings of this study also support that peer social support may buffer the effects of child physical abuse on adolescents’ emotional and social problems