Refractory insulin resistance and hemophagocytic lymphohistiocytosis following enfortumab vedotin treatment: A case report.

The increasing incidence of urothelial carcinoma, coupled with advancements in its therapeutic landscape, has resulted in improved survival rates for patients. This, in turn, has led to a growing population of patients requiring specialized oncological care, with Enfortumab vedotin (EV) emerging as a pivotal treatment for metastatic urothelial carcinoma. While EV is associated with hyperglycemia, ketoacidosis is exceedingly rare. To the best of our knowledge, the link between EV and hemophagocytic lymphohistiocytosis (HLH) has not yet been explored. A 56-year-old patient diagnosed with metastatic urothelial carcinoma underwent EV treatment as a third-line treatment after progression following treatment with cisplatin/gemcitabine and pembrolizumab. Notably, after receiving two doses of EV, the patient exhibited refractory insulin resistance, leading to ketoacidosis. Subsequently, HLH emerged, necessitating a treatment regimen involving dexamethasone and etoposide. Despite intensive efforts, the patient experienced septic shock, resulting in death. The present case report highlights refractory insulin resistance and ketoacidosis, followed by reactive HLH, in the context of EV therapy. The limited literature on these complications demonstrates the need for further research to improve the understanding of the underlying mechanisms. With growing evidence of the efficacy of EV and evolving survival rates in urothelial carcinoma, healthcare professionals must remain vigilant for potential adverse effects, ensuring early recognition and optimal patient care.

Effects of MAT1-2 Spore Ratios on Fruiting Body Formation and Degeneration in the Heterothallic Fungus Cordyceps militaris.

The medicinal mushroom Cordyceps militaris is widely exploited in traditional medicine and nutraceuticals in Asian countries. However, fruiting body production in C. militaris is facing degeneration through cultivation batches, and the molecular mechanism of this phenomenon remains unclear. This study showed that fruiting body formation in three different C. militaris strains, namely G12, B12, and HQ1, severely declined after three successive culturing generations using the spore isolation method. PCR analyses revealed that these strains exist as heterokaryons and possess both the mating-type loci, MAT1-1 and MAT1-2. Further, monokaryotic isolates carrying MAT1-1 or MAT1-2 were successfully separated from the fruiting bodies of all three heterokaryotic strains. A spore combination of the MAT1-1 monokaryotic isolate and the MAT1-2 monokaryotic isolate promoted fruiting body formation, while the single monokaryotic isolates could not do that themselves. Notably, we found that changes in ratios of the MAT1-2 spores strongly influenced fruiting body formation in these strains. When the ratios of the MAT1-2 spores increased to more than 15 times compared to the MAT1-1 spores, the fruiting body formation decreased sharply. In contrast, when MAT1-1 spores were increased proportionally, fruiting body formation was only slightly reduced. Our study also proposes a new solution to mitigate the degeneration in the heterokaryotic C. militaris strains caused by successive culturing generations.

Retroperitoneal ectopic pregnancy: successful expectant management in condition of early pregnancy failure.

BACKGROUND: Retroperitoneal ectopic pregnancy (REP) refers to abnormal implantation of the fertilized egg in the retroperitoneal cavity. REP can be divided into pelvic and abdominal positions. Extremely rare, the incidence of REP is less than 1% of ectopic pregnancy (EP). Herein, we report the first case of paraaortic-located REP in association with successful expectant management, thus raising awareness among healthcare providers, particularly in low-resource settings. CASE PRESENTATION: A reproductive-age woman presented at our tertiary referral hospital because of amenorrhea and a positive pregnancy test. Based on serial serum ß-hCG levels and imaging modalities including transabdominal ultrasound, transvaginal sonography, and magnetic resonance imaging (MRI), a REP of 7-9 weeks of gestational age adherent to abdominal paraaortic region was detected. Since the pregnancy was spontaneously arrested without clinical symptoms, expectant management was first indicated following careful evaluation. After a 1-month follow-up, the ectopic mass naturally degenerated without complications and her ß-hCG concentration returned to a negative value. Therefore, the patient recovered completely and avoided unnecessary surgery as well as toxicity of medical treatment when using systemic methotrexate. CONCLUSIONS: In addition to transvaginal and transabdominal ultrasound, MRI is necessary for the diagnosis of nonviable REP. Alongside the great vessels in the abdominal cavity should be taken into consideration in all suspected cases relating to this rare entity. Expectant management may be carefully indicated in conditions of nonviable REP and unruptured REP, where applicable.

Lipectomy for madelung disease using tumescent technique: a cross-sectional study.

Madelung's disease is a rare disfiguring disorder that affects both function and esthetic appearance in the head and/or shoulder, neck, and arms regions. Lipectomy is typically necessary but such treatment can encounter difficulties due to the large sizes of the tumors, interspersed with important organs in the surrounding region. In this report, the authors evaluate the effectiveness of using tumescent solution in lipectomy to provide a dual treatment of tissue removal for Madelung disease in the head-and-neck region. Methods: A prospective study and clinical descriptions were conducted on 17 patients undergoing 26 head-and-neck lipectomies. A tumescent solution was injected into the surgical region with a blunt-tip cannula 5-10 min before skin incision. The authors recorded systemic manifestations both during and after surgery; tumescent volume; surgical region; clarity of the operative field; weight of fat removed, and early complications. After surgery, the authors followed the patients from periods of 3 months to 4 years. Results: All 17 male patients had a history of alcoholism. In total, 12 lipectomies for the removal of anterior neck fatty masses and 14 lipectomies for the removal of posterior neck fatty masses were performed. The average amount of tumescent injected was 260.1 ml (range 140-550 ml). Surgery was reported as totally bloodless in 10 (38.5%) operative fields, with minimum bleeding in 12 (46.1%) operative fields, acceptable bleeding in four (15.4%) operative fields. The average surgical time was 175.6 min (range 135-250 min). The removed fatty masses weighed between 250 and 2150 g, with an average of 582.9 g. Early complications were seen in four patients, accounting for 15.4% (2 hematoma, 1 skin necrosis, and 1 seroma). Conclusions: Using tumescent solution in lipectomies to treat Madelung disease in the head and neck area is a simple, safe, and useful technique. The technique helps to create a clean operative field, reduces bleeding, and thereby assists surgeons during the operation.

Rectal Ectopic Pregnancy Managed Successfully by Minimally Invasive Treatment Using Local Methotrexate Injection and Systemic Methotrexate Administration: An Extremely Rare Case at Tu Du Hospital in Vietnam and Literature Review.

Rectal ectopic pregnancy (REP) is one of the most extremely rare forms of ectopic pregnancy that strongly leads to maternal mortality higher than common types. An early diagnosis of unruptured REP remains a challenge and its management ought to be individualized depending on the clinical scenario. Currently, owing to the paucity of data, there are no practical guidelines for an appropriate treatment until today. We hereby present a very unusual case at our maternity care center. A 30-year-old pregnant woman (gravidity: 2, parity: 2) complained with abdominal pain and retard menstrual cycle. After serum beta-human chorionic gonadotropin (ß-hCG) levels and ultrasonic examinations, a diagnosis of ovarian ectopic pregnancy was established. Thus, the patient underwent explanatory laparoscopy for confirming the diagnosis and for the treatment. However, on the 5th day postoperative course, her ß-hCG level continued to increase every 48 hours. By magnetic resonance imaging and pelvic ultrasonography, a gestational sac adherent to the rectal wall was clearly detected. After counseling with multidisciplinary team, a minimally invasive laparoscopy followed by a local injection of methotrexate under ultrasound guidance for gestational sac access and a systemic multidose methotrexate regimen were indicated. In result, her serum ß-hCG declined substantially. Although it is very rare, extrauterine pregnancy involving the rectum may be presented. Early diagnosis helps in avoiding the fatal complications and a proper management should be counseled carefully. Conservative treatment with minimally surgical intervention could be an alternative option in appropriate condition. Further data are required to summarize this occult entity.

The Intricate Interplay between the ZNF217 Oncogene and Epigenetic Processes Shapes Tumor Progression.

The oncogenic transcription factor ZNF217 orchestrates several molecular signaling networks to reprogram integrated circuits governing hallmark capabilities within cancer cells. High levels of ZNF217 expression provide advantages to a specific subset of cancer cells to reprogram tumor progression, drug resistance and cancer cell plasticity. ZNF217 expression level, thus, provides a powerful biomarker of poor prognosis and a predictive biomarker for anticancer therapies. Cancer epigenetic mechanisms are well known to support the acquisition of hallmark characteristics during oncogenesis. However, the complex interactions between ZNF217 and epigenetic processes have been poorly appreciated. Deregulated DNA methylation status at ZNF217 locus or an intricate cross-talk between ZNF217 and noncoding RNA networks could explain aberrant ZNF217 expression levels in a cancer cell context. On the other hand, the ZNF217 protein controls gene expression signatures and molecular signaling for tumor progression by tuning DNA methylation status at key promoters by interfering with noncoding RNAs or by refining the epitranscriptome. Altogether, this review focuses on the recent advances in the understanding of ZNF217 collaboration with epigenetics processes to orchestrate oncogenesis. We also discuss the exciting burgeoning translational medicine and candidate therapeutic strategies emerging from those recent findings connecting ZNF217 to epigenetic deregulation in cancer.

Multiple Symmetric Lipomatosis: Lipectomy for Madelung Collar.

Multiple symmetric lipomatosis (MSL) is a rare disease associated with metabolic disorders and alcoholism. In this report, we describe the clinical outcome and surgical protocol for eight men with Madelung collar who underwent treatment in a craniofacial and plastic surgery facility in Hanoi, Vietnam, between May 2018 and December 2020. We discuss the patients' clinical symptoms, subclinical signs, epidemiology, magnetic resonance imaging, computerized tomography, surgical protocol, complications, and postoperative indicators that we collected and evaluated. Each patient underwent surgery in two stages (i.e., in supine and prone positions). We injected a tumescent solution 10 min before the incision. Two surgeons performed each operation simultaneously. After surgery, we followed the patients for 6-27 months. All of the patients had a history of long-time alcohol abuse and had associated comorbidities that included liver disease, blood disorders, restricted neck movement, and orthopnea. We did not have to open the trachea or transfuse blood during any of the surgical procedures. Postoperatively, all patients were satisfied with their functional results and aesthetic appearance. One patient experienced a recurrence of his MSL. We believe our surgical protocol provides optimal results for patients with MSL and Madelung collar.

Penicillium digitatum as a Model Fungus for Detecting Antifungal Activity of Botanicals: An Evaluation on Vietnamese Medicinal Plant Extracts.

Medicinal plants play important roles in traditional medicine, and numerous compounds among them have been recognized for their antimicrobial activity. However, little is known about the potential of Vietnamese medicinal plants for antifungal activity. In this study, we examined the antagonistic activity of twelve medicinal plant species collected in Northern Vietnam against Penicillium digitatum, Aspergillus flavus, Aspergillus fumigatus, and Candida albicans. The results showed that the antifungal activities of the crude extracts from Mahonia bealei, Ficus semicordata, and Gnetum montanum were clearly detected with the citrus postharvest pathogen P. digitatum. These extracts could fully inhibit the growth of P. digitatum on the agar medium, and on the infected citrus fruits at concentrations of 300-1000 µg/mL. Meanwhile, the other tested fungi were less sensitive to the antagonistic activity of the plant extracts. In particular, we found that the ethanolic extract of M. bealei displayed a broad-spectrum antifungal activity against all four pathogenic fungi. Analysis of this crude extract by enrichment coupled with high-performance liquid chromatography revealed that berberine and palmatine are major metabolites. Additional inspections indicated berberine as the key compound responsible for the antifungal activity of the M. bealei ethanolic extract. Our study provides a better understanding of the potential of Vietnamese medicinal plant resources for combating fungal pathogens. This work also highlights that the citrus pathogen P. digitatum can be employed as a model fungus for screening the antifungal activity of botanicals.

Air pollution and risk of respiratory and cardiovascular hospitalizations in a large city of the Mekong Delta Region.

It is important to explore air pollution and health effects in developing cities for early prevention rather than waiting for conditions to deteriorate as in the current megacities. This study aims to investigate the short-term health effects of air pollution in a large city in the Mekong Delta Region (MDR) of Vietnam. Air pollution data from January 2015 to December 2018 were collected from the Environmental Monitoring Centre of Can Tho City. The data of respiratory and cardiovascular disease (CVD) admissions in 18 hospitals and medical centers were collected. A time-series regression analysis was conducted using distributed lag models to examine the relationship between the air pollutants and hospitalizations including the delayed effect up to 7 days. The research findings reveal that a 10 µg increase in PM10 was associated with an increase of 2.5% in the risk of respiratory admission for all people and 2.2% in the risk of CVD admission for the elderly on the same day. The analysis stratified by age and sex indicates that PM10 resulted in a higher risk of respiratory admission among children (0-5 years old) and males compared with other groups. PM10 and NO2 were significantly associated with CVD admission among the elderly at lag 4 and 6 days. The effects of other air pollutants (SO2, O3) were not observed in this study. As development continues in this region, there is an urgent need for intervention measures to minimize the health impacts associated with the expected increases in air pollution in the MDR.

Exploring the Significance of the Exon 4-Skipping Isoform of the ZNF217 Oncogene in Breast Cancer.

Oncogene alternative splicing events can create distinct functional transcripts that offer new candidate prognostic biomarkers for breast cancer. ZNF217 is a well-established oncogene but its exon 4-skipping isoform (ZNF217-ΔE4) has never been investigated in terms of clinical or biological relevance. Using in silico RNA-seq and RT-qPCR analyses, we demonstrated for the first time the existence of ZNF217-ΔE4 transcripts in primary breast tumors, and a positive correlation between ZNF217-ΔE4 mRNA levels and those of the wild-type oncogene (ZNF217-WT). A pilot retrospective analysis revealed that, in the Luminal subclass, the combination of the two ZNF217 variants (the ZNF217-ΔE4-WT gene-expression signature) provided more information than the mRNA expression levels of each isoform alone. Ectopic overexpression of ZNF217-ΔE4 in breast cancer cells promoted an aggressive phenotype and an increase in ZNF217-WT expression levels that was inversely correlated with DNA methylation of the ZNF217 gene. This study provides new insights into the possible role of the ZNF217-ΔE4 splice variant in breast cancer and suggests a close interplay between the ZNF217-WT and ZNF217-ΔE4 isoforms. Our data suggest that a dual signature combining the expression levels of these two isoforms may serve as a novel prognostic biomarker allowing better stratification of breast cancers with good prognosis and aiding clinicians in therapeutic decisions.

In vitro antiviral activities of ethanol and aqueous extracts of Vietnamese traditional medicinal plants against Porcine Epidemic Diarrhea virus: a coronavirus family member.

Porcine epidemic diarrhea virus (PEDV) causes diarrhea in pigs leading to severe illnesses and high mortality rates. The development of medicinal agents to treat PEDV infection is therefore crucial. In this study, antiviral activities against PEDV of ethanol and aqueous extracts of 17 Vietnamese traditional medicinal plants were evaluated using the cytopathic effect-based assay. The results showed that 14 out of 17 medicinal plants could inhibit the cytopathic effect of PEDV. The ethanol extract of Stixis scandens was identified as the most active extract with its MIC (minimum inhibitory concentration) being 0.15 µg/mL. Other plant extracts also displayed strong antiviral activity against PEDV, including Anisomeles indica, Pericampylus glaucus and Croton kongensis. The results demonstrate that certain medicinal plants have a high antiviral potential and may serve as a lead to develop novel pharmaceutical agents to cure PED as well as the diseases caused by other coronaviruses.

A newly constructed Agrobacterium-mediated transformation system revealed the influence of nitrogen sources on the function of the LaeA regulator in Penicillium chrysogenum.

Penicillium chrysogenum is not only an industrially important filamentous fungus for penicillin production, but it also represents as a promising cell factory for production of natural products. Development of efficient transformation systems with suitable selection markers is essential for genetic manipulations in P. chrysogenum. In this study, we have constructed a new and efficient Agrobacterium tumefaciens-mediated transformation (ATMT) system with two different selection markers conferring the resistance to nourseothricin and phleomycin for P. chrysogenum. Under the optimized conditions for co-cultivation at 22 °C for 60 h with acetosyringone concentration of 200 µM, the transformation efficiency of the ATMT system could reach 5009 ± 96 transformants per 106 spores. The obtained transformants could be exploited as the T-DNA insertion mutants for screening genes involved in morphogenesis and secondary metabolism. Especially, the constructed ATMT system was applied successfully to generate a knockout mutant of the laeA regulatory gene and relevant complementation strains in a wild strain of P. chrysogenum. Our results indicated that the LaeA regulator controls growth, sporulation, osmotic stress response and antibiotic production in P. chrysogenum, but its function is reliant on nitrogen sources. Furthermore, we showed that the laeA orthologous genes from the citrus postharvest pathogen P. digitatum and from the industrial fungus Aspergillus niger could recover the phenotypic defects in the P. chrysogenum laeA deletion mutant. Conclusively, this work provides a new ATMT system, which can be employed for T-DNA insertional mutagenesis, heterologous gene expression or for molecular inspections of potential genes related to secondary metabolism in P. chrysogenum.

Enhanced uptake of potassium or glycine betaine or export of cyclic-di-AMP restores osmoresistance in a high cyclic-di-AMP Lactococcus lactis mutant.

The broadly conserved bacterial signalling molecule cyclic-di-adenosine monophosphate (c-di-AMP) controls osmoresistance via its regulation of potassium (K+) and compatible solute uptake. High levels of c-di-AMP resulting from inactivation of c-di-AMP phosphodiesterase activity leads to poor growth of bacteria under high osmotic conditions. To better understand how bacteria can adjust in response to excessive c-di-AMP levels and to identify signals that feed into the c-di-AMP network, we characterised genes identified in a screen for osmoresistant suppressor mutants of the high c-di-AMP Lactococcus ΔgdpP strain. Mutations were identified which increased the uptake of osmoprotectants, including gain-of-function mutations in a Kup family K+ importer (KupB) and inactivation of the glycine betaine transporter transcriptional repressor BusR. The KupB mutations increased the intracellular K+ level while BusR inactivation increased the glycine betaine level. In addition, BusR was found to directly bind c-di-AMP and repress expression of the glycine betaine transporter in response to elevated c-di-AMP. Interestingly, overactive KupB activity or loss of BusR triggered c-di-AMP accumulation, suggesting turgor pressure changes act as a signal for this second messenger. In another group of suppressors, overexpression of an operon encoding an EmrB family multidrug resistance protein allowed cells to lower their intracellular level of c-di-AMP through active export. Lastly evidence is provided that c-di-AMP levels in several bacteria are rapidly responsive to environmental osmolarity changes. Taken together, this work provides evidence for a model in which high c-di-AMP containing cells are dehydrated due to lower K+ and compatible solute levels and that this osmoregulation system is able to sense and respond to cellular water stress.

A highly efficient Agrobacterium tumefaciens-mediated transformation system for the postharvest pathogen Penicillium digitatum using DsRed and GFP to visualize citrus host colonization.

Penicillium digitatum is a major postharvest pathogen of citrus crops. This fungus broadly spreads worldwide and causes green mold disease, which results in severe losses for citrus production. Understanding of the citrus infection by P. digitatum may help develop effective strategies for controlling this pathogen. In this study, we have characterized a virulent strain of P. digitatum isolated in Vietnam and established a highly efficient Agrobacterium tumefaciens-mediated transformation (ATMT) system for this fungal strain with two newly constructed binary vectors. These binary vectors harbor dominant selectable markers for hygromycin or nourseothricin resistance, and expression cassettes for the red fluorescent protein (DsRed) or the green fluorescent protein (GFP), respectively. Using the established ATMT system, the transformation efficiency of the Vietnamese strain could reach a very high yield of 1240±165 transformants per 106 spores. Interestingly, we found that GFP is much better than DsRed for in situ visualization of citrus fruit colonization by the fungus. Additionally, we showed that the transformation system can also be used to generate T-DNA insertion mutants for screening non-pathogenic or less virulent strains. Our work provides a new platform including a virulent tropical strain of P. digitatum, an optimized ATMT method and two newly constructed binary vectors for investigation of the postharvest pathogen. This platform will help develop strategies to dissect molecular mechanisms of host-pathogen interactions in more detail as well as to identify potential genes of pathogenicity by either insertional mutagenesis or gene disruption in this important pathogenic fungus.

TCF7L1 promotes skin tumorigenesis independently of ß-catenin through induction of LCN2.

The transcription factor TCF7L1 is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in skin tumorigenesis has not yet been defined. Here we document TCF7L1 upregulation in skin squamous cell carcinoma (SCC) and demonstrate that TCF7L1 overexpression increases tumor incidence, tumor multiplicity, and malignant progression in the chemically induced mouse model of skin SCC. Additionally, we show that downregulation of TCF7L1 and its paralogue TCF7L2 reduces tumor growth in a xenograft model of human skin SCC. Using separation-of-function mutants, we show that TCF7L1 promotes tumor growth, enhances cell migration, and overrides oncogenic RAS-induced senescence independently of its interaction with ß-catenin. Through transcriptome profiling and combined gain- and loss-of-function studies, we identified LCN2 as a major downstream effector of TCF7L1 that drives tumor growth. Our findings establish a tumor-promoting role for TCF7L1 in skin and elucidate the mechanisms underlying its tumorigenic capacity.

A new and efficient approach for construction of uridine/uracil auxotrophic mutants in the filamentous fungus Aspergillus oryzae using Agrobacterium tumefaciens-mediated transformation.

Aspergillus oryzae is a filamentous fungus widely used in food industry and as a microbial cell factory for recombinant protein production. Due to the inherent resistance of A. oryzae to common antifungal compounds, genetic transformation of this mold usually requires auxotrophic mutants. In this study, we show that Agrobacterium tumefaciens-mediated transformation (ATMT) method is very efficient for deletion of the pyrG gene in different Aspergillus oryzae wild-type strains to generate uridine/uracil auxotrophic mutants. Our data indicated that all the obtained uridine/uracil auxotrophic transformants, which are 5- fluoroorotic acid (5-FOA) resistant, exist as the pyrG deletion mutants. Using these auxotrophic mutants and the pyrG selectable marker for genetic transformation via A. tumefaciens, we could get about 1060 transformants per 106 fungal spores. In addition, these A. oryzae mutants were also used successfully for expression of the DsRed fluorescent reporter gene under control of the A. oryzae amyB promoter by the ATMT method, which resulted in obvious red transformants on agar plates. Our work provides a new and effective approach for constructing the uridine/uracil auxotrophic mutants in the importantly industrial fungus A. oryzae. This strategy appears to be applicable to other filamentous fungi to develop similar genetic transformation systems based on auxotrophic/nutritional markers for food-grade recombinant applications.

Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2.

Cell migration is an integral part of re-epithelialization during skin wound healing, a complex process involving molecular controls that are still largely unknown. Here we identify a novel role for Tcf3, an essential transcription factor regulating embryonic and adult skin stem cell functions, as a key effector of epidermal wound repair. We show that Tcf3 is upregulated in skin wounds and that Tcf3 overexpression accelerates keratinocyte migration and skin wound healing. We also identify Stat3 as an upstream regulator of Tcf3. We show that the promigration effects of Tcf3 are non-cell autonomous and occur independently of its ability to interact with ß-catenin. Finally, we identify lipocalin-2 as the key secreted factor downstream of Tcf3 that promotes cell migration in vitro and wound healing in vivo. Our findings provide new insights into the molecular controls of wound-associated cell migration and identify potential therapeutic targets for the treatment of defective wound repair.

Cost of Illness of Chronic Hepatitis B Infection in Vietnam.

OBJECTIVES: To estimate the total financial burden of chronic hepatitis B virus (HBV) infection for Vietnam by quantifying the direct medical, the direct nonmedical, and indirect costs among patients with various stages of chronic HBV infection. METHODS: Direct medical cost data were retrieved retrospectively from medical histories of inpatients and outpatients in 2008 from a large referral hospital in Hanoi, Vietnam. Direct nonmedical and indirect costs data were obtained from face-to-face interviews of outpatients from the same hospital. The treatment cost per patient per chronic HBV infection stage was multiplied by the total estimated patients in Vietnam to get the total cost of illness for the nation. RESULTS: Nationally, the total cost attributable to chronic HBV infection and its complications in 2008 was estimated to be approximately US $4.4 billion, with the direct medical cost accounting for about 70% of that estimate. The cost of antivirals was the major cost driver in treating chronic HBV infection. The per-patient total annual direct medical cost increased with the severity of the disease, with the estimated costs for chronic HBV infection and hepatocellular carcinoma as US $450.35 and US $1883.05, respectively. When compared with the 2008 per-capita gross domestic product of ∼US $1024, the financial burden of treating chronic HBV infection is very high in Vietnam. CONCLUSIONS: This study confirmed that chronic HBV infection poses a significant financial burden for the average patient and that lacking treatment would become a social issue in Vietnam. Although HBV vaccination has been universally implemented, more health care investment and the greater availability of affordable medications are still needed to attain equity in proper treatment for patients with HBV infection.

IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway.

IQGAP1 is a conserved modular protein overexpressed in cancer and involved in organizing actin and microtubules in motile processes such as adhesion, migration, and cytokinesis. A variety of proteins have been shown to interact with IQGAP1, including the small G proteins Rac1 and Cdc42, actin, calmodulin, beta-catenin, the microtubule plus end-binding proteins CLIP170 (cytoplasmic linker protein) and adenomatous polyposis coli. However, the molecular mechanism by which IQGAP1 controls actin dynamics in cell motility is not understood. Quantitative co-localization analysis and down-regulation of IQGAP1 revealed that IQGAP1 controls the co-localization of N-WASP with the Arp2/3 complex in lamellipodia. Co-immunoprecipitation supports an in vivo link between IQGAP1 and N-WASP. Pull-down experiments and kinetic assays of branched actin polymerization with N-WASP and Arp2/3 complex demonstrated that the C-terminal half of IQGAP1 activates N-WASP by interacting with its BR-CRIB domain in a Cdc42-like manner, whereas the N-terminal half of IQGAP1 antagonizes this activation by association with a C-terminal region of IQGAP1. We propose that signal-induced relief of the autoinhibited fold of IQGAP1 allows activation of N-WASP to stimulate Arp2/3-dependent actin assembly.