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Hydrogels are crosslinked polymer chains with three-dimensional (3D) network structures, which can absorb relatively large amounts of fluid. Because of the high water content, soft structure, and porosity of hydrogels, they closely resemble living tissues. Research in recent years shows that hydrogels have been applied in various fields, such as agriculture, biomaterials, the food industry, drug delivery, tissue engineering, and regenerative medicine. Along with the underlying technology improvements of hydrogel development, hydrogels can be expected to be applied in more fields. Although not all hydrogels have good biodegradability and biocompatibility, such as synthetic hydrogels (polyvinyl alcohol, polyacrylamide, polyethylene glycol hydrogels, etc.), their biodegradability and biocompatibility can be adjusted by modification of their functional group or incorporation of natural polymers. Hence, scientists are still interested in the biomedical applications of hydrogels due to their creative adjustability for different uses. In this review, we first introduce the basic information of hydrogels, such as structure, classification, and synthesis. Then, we further describe the recent applications of hydrogels in 3D cell cultures, drug delivery, wound dressing, and tissue engineering.

Clinical presentations of dengue fever (DF) are diverse and non-specific, causing unpredictable progression and outcomes. Its progression and severity have been associated with cytokine levels alteration. In this study, dengue patients were classified into groups following the 2009 WHO dengue classification scheme to investigate the cytokine signature at different severity of the disease: dengue without warning sign symptoms (A); dengue with warning signs (B); severe dengue (C); other fever (OF) and healthy (Healthy). We analyzed 23 different cytokines simultaneously, namely IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-33, CD14, CD54, CD62E, CD62L, CD62p, CD106, CD121b, CD154, CD178, GM-CSF, IFN-g, MIF, ST2 and TNF from patients admitted to National Cheng Kung University Hospital during the 2015 Taiwan dengue outbreak. Cytokines TNF, CD54, CD62E, CD62L, CD62P, GM-CSF, IL-1b, IL-2, IL-6, IL-8, IL-10, IL-12p70, IL-17A, INF-g and MIF were elevated while CD106, CD154, IL-4 and L-33 were decreased when compared to the control. IL-10 demonstrated to be a potential diagnostic marker for DF (H and A group; AUC = 0.944, H and OF group; AUC = 0.969). CD121b demonstrated to be predictive of the SD (A and B group; AUC = 0.744, B and C group; AUC = 0.775). Our results demonstrate the cytokine profile changes during the progression of dengue and highlight possible biomarkers for optimizing effective intervention strategies.

Background Initial symptoms of dengue fever are non-specific, and thus definite diagnosis requires laboratory confirmation. Detection of IgM against dengue virus (DENV) has become widely used for dengue diagnosis. Understanding the persistence of anti-DENV IgM in subjects after acute infection is essential in order to interpret test results correctly. Although the longevity of anti-DENV IgM has been vehemently investigated in symptomatic children, anti-DENV IgM persistence in adults and in asymptomatically infected people have seldom been reported. Methods We prospectively investigated 44 adults with detectable anti-DENV IgM in a serosurvey conducted in the 2015 dengue epidemic in Tainan, Taiwan. Among subjects within the cohort, 17 were classified to be symptomatic and 27 were asymptomatic. The enzyme-linked immunosorbent assay (ELISA) from Standard Diagnostic (SD) and Focus Diagnostic were used to detect anti-DENV IgM for specimens collected initially, at 6 and 12 months. Regression analyses were used to estimate the duration of anti-DENV IgM fell below the detectable level. Rapid dengue tests from Standard Diagnostics had been widely adopted to detect anti-DENV IgM in Taiwan during the 2015 dengue outbreak. As such, collected specimens were also evaluated with the SD rapid dengue test in parallel. Results Anti-DENV IgM was detectable in 70.5 and 46.2% of the 44 subjects at 6 months and 12 months by the SD ELISA, respectively, while 13.6 and 7.7%, respectively, by the Focus ELISA. There was no significant difference in anti-DENV IgM detection for the follow-up specimens between subjects with symptomatic and asymptomatic infections. The regression analysis estimated that anti-DENV IgM persistence fell to the undetectable level at 338.3 days (95% CI 279.7–446.9) by SD ELISA, while at 175.7 days (95% CI 121.9–221.1) by Focus ELISA. The detectable frequency of anti-DENV IgM by rapid tests was 86.4%, 68.2 and 35.9% at initial, 6 and 12 months, respectively. Conclusion Anti-DENV IgM was found to persist much longer than previously thought, suggesting a necessity of re-evaluation of the use of anti-DENV IgM for both the diagnosis of dengue and serological surveillance, especially when large outbreaks have occurred in the preceding year.

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of these proteins by ACE inhibitors may contribute to the amelioration of cognitive deficits in Alzheimer’s disease/dementia, as well as the clinically observed deceleration of functional decline in Alzheimer’s patients. This discovery suggests that the supplementation of ACE inhibitors may promote neuronal cell survival independently of their antihypertensive effect. Overall, these findings indicate that ACE inhibitors may be a promising avenue for developing effective treatments for Alzheimer’s disease.

Although dengue virus (DENV) can establish infections in hematopoietic stem progenitor cells (HSPCs), there is little information on dengue virus persistent infection in CD34+ and CD133+ cell surface glycoproteins of hematopoietic stem cells (HSCs). CD34 and CD133 also function as cell–cell adhesion factors, which are present in umbilical cord blood (UCB). In this study, we sought to establish a persistent infection model of DENV infection in UCB using a prolonged period of infection lasting 30 days. Post-infection, the results exhibited a productive and non-productive phase of DENV production. Using a plaque assay, Western blot, and confocal microscopy, we demonstrated that CD133 and CD34 cells are target cells for DENV infection. Moreover, we showed that DENV particles can be recovered from the non-productive phase of DENV-infected CD34 and CD133 cells after co-incubation with Vero cells. We concluded that CD133 and CD34 retain their capacity to produce the infectious virus due to proliferation and their ability to repopulate, as deduced from a BrdU proliferation assay and flow cytometry analysis using t-distributed stochastic neighbor embedding. In summary, the platform to co-culture infected primitive HSCs from their non-productive phase onto Vero cells will give new insights into understanding the DENV dynamics in cell-to-cell transmission and reactivation of the virus.

Background A severe dengue epidemic occurred in 2015 which resulted in over 22,000 laboratory-confirmed cases. A cross-sectional seroprevalence study was conducted during the ending phase of this epidemic to evaluate the true incidence of dengue virus (DENV) infection and the level of herd immunity. Methods Adult residents in three administrative districts with high dengue incidence were recruited; workers in two districts with intermediate dengue incidence were also recruited for comparison. DENV-specific IgM and IgG were tested using commercial enzyme-linked immunosorbent assays. DENV RNA was detected using commercial quantitative real-time reverse transcriptase polymerase chain reaction assay. Univariate and multivariate logistic regressions were performed to identify risk factors for recent and past DENV infection. Results The overall seroprevalence of anti-DENV IgM and IgG in 1391 participants was 6.8 and 17.4%, respectively. The risk of recent DENV infection increased with age, with the elderly having the highest risk of infection. Living in areas with high incidence of reported dengue cases and having family members being diagnosed with dengue in 2015 were also independent risk factors for recent DENV infection. One sample was found to have asymptomatic viremia with viral load as high as 10 5 PFU/ml. Conclusions Comparing the seroprevalence of anti-DENV IgM with the incidence of reported dengue cases in 2015, we estimated that 1 out of 3.7 dengue infections were reported to the surveillance system; widespread use of rapid diagnostic tests might contribute to this high reporting rate. The results also indicate that the overall herd immunity remains low and the current approved Dengvaxia® is not quite suitable for vaccination in Taiwan.

Background We recently conducted a serosurvey of newly arrived workers in Taiwan from four Southeast Asian countries which revealed that 1% of the migrant workers had laboratory-confirmed recent Zika virus (ZIKV) infection. Taiwan, where Aedes mosquitoes are prevalent, has a close relationship with Southeast Asian countries. Up to now, 21 imported cases of ZIKV infection have been reported in Taiwan, but there has been no confirmed indigenous case. The aim of this serosurvey was to assess whether there was unrecognized ZIKV infections in Taiwan. Methods A total of 212 serum samples collected in a cross-sectional seroepidemiologic study conducted during the end of the 2015 dengue epidemic in Tainan, Taiwan, were analyzed. Anti-ZIKV IgM and IgG were tested using commercial enzyme-linked immunosorbent assays (ELISAs). Plaque reduction neutralization tests (PRNTs) for ZIKV and four dengue virus (DENV) serotypes were performed for samples with positive anti-ZIKV antibodies. A confirmed case of ZIKV infection was defined by ZIKV PRNT 90 titer ratio ≥ 4 compared to four DENV serotypes. Results The mean age of the 212 participants was 54.0 years (standard deviation 13.7 years), and female was predominant (67.0%). Anti-ZIKV IgM and IgG were detected in 0 (0%) and 9 (4.2%) of the 212 participants, respectively. For the 9 samples with anti-ZIKV IgG, only 1 sample had 4 times higher ZIKV PRNT 90 titers compared to PRNT 90 titers against four dengue virus serotypes; this individual denied having traveled abroad. Conclusions The results suggest that undetected indigenous ZIKV transmission might have occurred in Taiwan. The findings also suggest that the threat of epidemic transmission of ZIKV in Taiwan does exist due to extremely low-level of herd immunity. Our study also indicates that serological tests for ZIKV-specific IgG remain a big challenge due to cross-reactivity, even in dengue non-endemic countries.

Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become the global challenge. Reaching global herd immunity will help end the COVID-19 pandemic. However, vaccine shortage and vaccine hesitancy are the obstacles to achieve global herd immunity against SARS-CoV-2. The current homologous vaccine regimen is experimentally switching to heterologous vaccination at several study sites. However, the reactogenicity of heterologous ChAdOx1-S and mRNA vaccination against SARS-CoV-2 is still unclear. We have conducted a systematic review to summarize the current findings on the safety and immunogenicity of this heterologous vaccination and elucidate their implications against SARS-CoV-2. This systematic review was conducted by the guidelines of PRISMA. Articles were searched from PubMed and other sources (MedRixv and Google scholar) starting from 1 January to 5 September 2021. The search term was heterologous ChAdOx1-S and BNT162b2 or mRNA-1273 vaccination. Our review found that participants with ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S did not have the serious adverse events seen with homologous vaccination. Participants with the heterologous regimen (ChAdOx1/BNT162b2, ChAdOx1-S/mRNA-1273 or BNT162b2/ChAdOx1-S), compared with those with two doses of ChAdOx1-S, have shown a more robust immune responses against SARS-CoV-2, such as higher levels of responsive antibodies or increased numbers of spike-specific T-cells. Nevertheless, these immune responses were slightly diminished in the recipients of BNT162b2/ChAdOx1-S. Also, the safety study of heterologous ChAdOx1-S/mRNA vaccination was based on small populations. Further studies to enclose diverse categories, such as race/ethnicity or geography, may be necessary. Overall, the heterologous immunization with ChAdOX1-S and the mRNA vaccine may improve the vaccine shortage related slow pace of reaching herd immunity, especially using the heterologous immunization with ChAdOx1-S/BNT162b2.

Background: Radiolabeled compounds can serve as diagnostic or therapeutic agents depending on the characteristics of the isotopes used. IMPY (6-iodo-2-(4′-dimethylamino)-phenyl-imidazo[1,2-a]pyridine) is a lipophilic derivative of thioflavin-T, designed to function as a tracer when labeled with radioactive iodine. While it has been primarily studied for imaging applications, its potential therapeutic effects when labeled with iodine-125 (125I) remain to be explored. Methods: In this study, IMPY was synthesized and labeled with 125I for therapeutic purposes. Three different labeling methods were employed: isotope exchange reaction, redox reaction, and the Iodogen technique. The radiochemical yield of each method was determined to identify the most effective approach. Additionally, the effects of 125I-IMPY on neuroblastoma cells were evaluated by assessing its toxicity and cellular uptake. Results: The radiochemical yields for the isotope exchange reaction, redox reaction, and Iodogen technique were found to be 0.96%, 10.74%, and 96.52%, respectively. The Iodogen technique exhibited the highest yield, exceeding 90% even after 48 h, making it the most efficient method. Furthermore, the impact of 125I-IMPY on neuroblastoma cells was analyzed, revealing significant cellular uptake and potential therapeutic effects. Conclusions: This study demonstrated that the Iodogen technique is the most effective method for labeling IMPY with 125I. The high labeling efficiency and observed cellular effects suggest that 125I-IMPY could be considered not only as a tracer but also as a potential therapeutic agent for neuroblastoma. Further studies are needed to explore its full therapeutic potential and mechanism of action.

Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.