Hepatitis B virus infection among pregnant women in Taiwan: Comparison between women born in Taiwan and other southeast countries

<p>Abstract</p> <p>Background</p> <p>Taiwan's national vaccination program has successfully decreased the prevalence of hepatitis B infection after twenty years of implementation and might be indirectly beneficial to the second generation. In this study, we compared the hepatitis B infection status of two groups: pregnant Taiwanese women and other Southeast Asian women, who because they had immigrated later in life to Taiwan by marriage to a Taiwanese man, had not been exposed to that vaccination program to evaluate the effect of hepatitis vaccination program on women of child-bearing age and further explored the potential impact of immigration on the hepatitis B public health policy in Taiwan.</p> <p>Methods</p> <p>Data was collected from 10,327 women born in Taiwan and 1,418 women born in other Southeast Asian countries, both groups receiving prenatal examinations at Fooyin University Hospital between 1996 and 2005. The results of serum hepatitis B s-Antigen (HBsAg) and hepatitis B e-Antigen (HBeAg) tests and other demographic data were obtained by medical chart review.</p> <p>Results</p> <p>The pregnant women from Taiwan had a higher HBsAg positive rate (15.5%) but lower HBeAg(+)/HBsAg(+) ratio (32.1%) than the women from other countries (8.9% and 52.4%). For those born before July, 1984, the period of no national vaccination program, Taiwanese women had a higher HBsAg positive rate than other Southeast Asian women (15.7% vs. 8.4%), but for women born after that day and before June 1986, the period of vaccination for high risk newborns, the HBsAg positive rates found to be slightly lower for Taiwanese women than for other Southeast Asian women (11.4% vs. 12.3%) and the difference was more significant (3.1% vs. 28.6%) after June 1986, the period of vaccination for all newborns. While the HBeAg(+)/HBsAg(+) ratios decreased with age in both groups, they were consistently higher in women from other Southeast Asian countries than in women born in Taiwan after age 20.</p> <p>Conclusion</p> <p>In Taiwan, the neonatal vaccination program that was implemented in 1984 has successfully reduced hepatitis B infection among pregnant women in present day, and is likely to indirectly prevent hepatitis B infection in the next generation. However, the increasing number of pregnant women from other Southeast Asian countries without a national neonatal vaccination program or with a program that was introduced later than the one in Taiwan will likely lessen the positive impact of this program and should be further assessed.</p

The crest phenotype in domestic chicken is caused by a 197 bp duplication in the intron of HOXC10

The Crest mutation in chicken shows incomplete dominance and causes a spectacular phenotype in which the small feathers normally present on the head are replaced by much larger feathers normally present only in dorsal skin. Using whole-genome sequencing, we show that the crest phenotype is caused by a 197 bp duplication of an evolutionarily conserved sequence located in the intron of HOXC10 on chromosome 33. A diagnostic test showed that the duplication was present in all 54 crested chickens representing eight breeds and absent from all 433 non-crested chickens representing 214 populations. The mutation causes ectopic expression of at least five closely linked HOXC genes, including HOXC10, in cranial skin of crested chickens. The result is consistent with the interpretation that the crest feathers are caused by an altered body region identity. The upregulated HOXC gene expression is expanded to skull tissue of Polish chickens showing a large crest often associated with cerebral hernia, but not in Silkie chickens characterized by a small crest, both homozygous for the duplication. Thus, the 197 bp duplication is required for the development of a large crest and susceptibility to cerebral hernia because only crested chicken show this malformation. However, this mutation is not sufficient to cause herniation because this malformation is not present in breeds with a small crest, like Silkie chickens

Caspase-8 inactivation drives autophagy-dependent inflammasome activation in myeloid cells.

Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd-/-Ripk3-/- myeloid cells promoted interleukin-1β (IL-1β) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd-/-Ripk3-/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1β/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic shock in Fadd-/-Ripk3-/- mice, implying distinct death processes in other cell types. Cathepsin-B contributes to IETD-mediated inflammasome activation, as its inhibition or down-regulation limited IETD-elicited IL-1β production. Therefore, the autophagy and cathepsin-B axis represents one of the pathways leading to atypical inflammasome activation when apoptosis and necroptosis are suppressed and capase-8 is inhibited in myeloid cells

TRPV1 is a Responding Channel for Acupuncture Manipulation in Mice Peripheral and Central Nerve System

Background/Aims: Acupuncture involves inserting a fine needle into a specific point, often called an acupoint, thereby initiating a therapeutic effect accompanied by phenomena such as soreness, heaviness, fullness, and numbness. Acupoints are characterized as points located in deep tissues with abundant sensory nerve terminals, which suggests that there is a strong relationship between acupoints and peripheral sensory afferents. In this study, we determined whether manual acupuncture (MA) or different frequencies of electroacupuncture (EA) share similar mechanisms for activating excitatory neurotransmission. Methods: We performed MA or EA at acupoint ST36 and we also used western blot and immunostaining techniques to determine neural changes at the peripheral dorsal root ganglion (DRG), spinal cord (SC), and somatosensory cortex (SSC) levels. Results: Our results show that either MA or EA at the ST36 acupoint significantly increased components of the TRPV1-related signaling pathway, such as pPKA, pPI3K, pPKC-pERK, and pAKT (but not pp38 or pJNK) at the peripheral DRG and central SC-SSC levels. Furthermore, excitatory phosphorylated N-methyl-D-aspartate receptor (pNMDA) and pCaMKIIα (but not pNR2B, pCaMKIIδ, or pCaMKIIγ) also increased. These molecules could not increase in the DRG and SC-SSC of TRPV1–/–mice. Conclusion: Our data demonstrates that both MA and EA can activate excitatory signals in either peripheral or central levels. We also define that TRPV1 is crucial for an acupuncture effect and then initiate excitatory pNR1-pCaMKII pathway, at peripheral DRG and central SC-SSC level. We suggest that the TRPV1 signaling pathway is highly correlated to Acupuncture effect that implies the real clinical significance

Nanofibrous insulin/vildagliptin core-shell PLGA scaffold promotes diabetic wound healing

Introduction: Slow wound repair in diabetes is a serious adverse event that often results in loss of a limb or disability. An advanced and encouraging vehicle is wanted to enhance clinically applicable diabetic wound care. Nanofibrous insulin/vildagliptin core-shell biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffolds to prolong the effective drug delivery of vildagliptin and insulin for the repair of diabetic wounds were prepared.Methods: To fabricate core-shell nanofibrous membranes, vildagliptin mixture with PLGA, and insulin solution were pumped via separate pumps into two differently sized capillary tubes that were coaxially electrospun.Results and Discussion: Nanofibrous core-shell scaffolds slowly released effective vildagliptin and insulin over 2 weeks in vitro migration assay and in vivo wound-healing models. Water contact angle (68.3 ± 8.5° vs. 121.4 ± 2.0°, p = 0.006) and peaked water absorbent capacity (376% ± 9% vs. 283% ± 24%, p = 0.003) of the insulin/vildagliptin core-shell nanofibrous membranes remarkably exceeded those of a control group. The insulin/vildagliptin-loaded core-shell nanofibers improved endothelial progenitor cells migration in vitro (762 ± 77 cells/mm2 vs. 424.4 ± 23 cells/mm2, p &lt; 0.001), reduced the α-smooth muscle actin content in vivo (0.72 ± 0.23 vs. 2.07 ± 0.37, p &lt; 0.001), and increased diabetic would recovery (1.9 ± 0.3 mm2 vs. 8.0 ± 1.4 mm2, p = 0.002). Core-shell insulin/vildagliptin-loaded nanofibers extend the drug delivery of insulin and vildagliptin and accelerate the repair of wounds associated with diabetes

Induction chemotherapy with dose-modified docetaxel, cisplatin, and 5-fluorouracil in Asian patients with borderline resectable or unresectable head and neck cancer

BackgroundSignificant ethnic differences in susceptibility to the effects of chemotherapy exist. Here, we retrospectively analyzed the safety and efficacy of induction chemotherapy (ICT) with dose-modified docetaxel, cisplatin, and 5-fluorouracil (TPF) in Asian patients with borderline resectable or unresectable head and neck squamous cell carcinoma (HNSCC).MethodsBased on the incidence of adverse events that occurred during daily practice, TPF90 (90% of the original TPF dosage; docetaxel 67.5 mg/m2 on Day 1, cisplatin 67.5 mg/m2 on Day 1, and 5-fluorouracil 675 mg/m2 on Days 1–5) was used for HNSCC patients who were scheduled to receive ICT TPF.ResultsBetween March 2011 and May 2014, 52 consecutive patients with borderline resectable or unresectable HNSCC were treated with ICT TPF90 followed by concurrent chemoradiotherapy. Forty-four patients (84.6%) received at least three cycles of ICT TPF90. The most commonly observed Grade 3–4 adverse events included neutropenia (35%), anemia (25%), stomatitis (35%), diarrhea (16%), and infections (13.5%). In an intention-to-treat analysis, the complete and partial response rates after ICT TPF90 were 13.5% and 59.6%, respectively. The complete and partial response rates following radiotherapy and salvage surgery were 42.3% and 25.0%, respectively. The estimated 3-year overall survival and progression-free survival rates were 41% [95% confidence interval (CI): 25–56%] and 23% (95% CI: 10–39%), respectively. The observed median overall survival and progression-free survival were 21.0 months (95% CI: 13.3–28.7 months) and 16.0 months (95% CI: 10.7–21.3 months), respectively.ConclusionTPF90 is a suitable option for Asian patients with borderline resectable or unresectable HNSCC who are scheduled for ICT

ABL Genomic Editing Sufficiently Abolishes Oncogenesis of Human Chronic Myeloid Leukemia Cells In Vitro and In Vivo

Chronic myelogenous leukemia (CML) is the most common type of leukemia in adults, and more than 90% of CML patients harbor the abnormal Philadelphia chromosome (Ph) that encodes the BCR-ABL oncoprotein. Although the ABL kinase inhibitor (imatinib) has proven to be very effective in achieving high remission rates and improving prognosis, up to 33% of CML patients still cannot achieve an optimal response. Here, we used CRISPR/Cas9 to specifically target the BCR-ABL junction region in K562 cells, resulting in the inhibition of cancer cell growth and oncogenesis. Due to the variety of BCR-ABL junctions in CML patients, we utilized gene editing of the human ABL gene for clinical applications. Using the ABL gene-edited virus in K562 cells, we detected 41.2% indels in ABL sgRNA_2-infected cells. The ABL-edited cells reveled significant suppression of BCR-ABL protein expression and downstream signals, inhibiting cell growth and increasing cell apoptosis. Next, we introduced the ABL gene-edited virus into a systemic K562 leukemia xenograft mouse model, and bioluminescence imaging of the mice showed a significant reduction in the leukemia cell population in ABL-targeted mice, compared to the scramble sgRNA virus-injected mice. In CML cells from clinical samples, infection with the ABL gene-edited virus resulted in more than 30.9% indels and significant cancer cell death. Notably, no off-target effects or bone marrow cell suppression was found using the ABL gene-edited virus, ensuring both user safety and treatment efficacy. This study demonstrated the critical role of the ABL gene in maintaining CML cell survival and tumorigenicity in vitro and in vivo. ABL gene editing-based therapy might provide a potential strategy for imatinib-insensitive or resistant CML patient