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Few support services and caregiving interventions exist to support family caregivers in low- and middle-income countries (LMIC). This paper presents exploratory analyses of outcomes of Resources for Enhancing Alzheimer's Caregiver Health in Vietnam (REACH VN).A cluster randomized controlled trial (RCT) was conducted in Soc Son, a semi-rural area in Hanoi. Nine clusters with 60 caregivers were randomized to either an enhanced control group or REACH VN, an in-home, multicomponent, family caregiver support intervention delivered over two to three months. Outcomes were assessed at baseline and three months.Caregivers in the intervention group experienced a significantly greater reduction in frustration levels compared to those in the control group. There were differences in other outcomes (e.g., care recipient problem behaviors and associated caregiver bother) favoring the intervention condition that did not reach statistical significance.We found additional evidence that REACH VN is a promising intervention to improve family caregiver outcomes in Vietnam.

Introduction: Comprehensive geriatric assessment (CGA) of older diabetic patients is thought to be of value, but there have been limited studies on the prevalence of impairments in the components of a CGA as well as the relationship between CGA and diabetic control in this group. Objective: This study aimed to evaluate the prevalence of components of CGA in older patients with diabetes in National Geriatric Hospital, Hanoi, Vietnam, and determine the association among domains of CGA with measures of diabetic control. Methods: A cross-sectional study of diabetic outpatients aged ≥60 years at National Geriatric Hospital in Hanoi, Vietnam, recruited over 3 months. The CGA questionnaire includes different assessments consisting of cognitive impairment (using Mini-Cog test), depression (using the 15-item Geriatric Depression Scale), urinary incontinence (using the 3-Incontinence questions), Activities of Daily Living (ADL) dependence, Instrumental Activities of Daily Living (IADL) dependence, high fall risk (using Hendrich II Fall Risk Model), hearing loss (using Whisper test), low visual acuity (using Snellen test), polypharmacy, malnutrition (using the Mini-Nutritional Assessment Short Form), and multiple geriatric conditions (patients had 2 or more geriatric conditions). Multiple logistic regression was used to analyze the association between demographic factors and CGA components with measures of diabetes control. Results: A total of 412 patients were recruited (56.6% female, mean age 71.9 [7.6] years). Prevalence of impairment in components of the CGA was high and highest for vision impairment (94.2%) and multiple geriatric conditions (89.3%). Age 130 mg/dL) and poor HbA1c control (≥7%). Conclusions: This study highlights that geriatric syndromes are common in older diabetic patients and associated with poorer diabetic control. It suggests CGA may be important to conduct in this group by establishing an interdisciplinary Geriatric health care team.

This study aims to provide data on usual walking speed in individuals aged 80 years or older and determine the association between walking speed and related factors in community-dwelling older adults. A cross-sectional study design was conducted to measure walking speed on community-dwelling elders aged 80 years or older in Soc Son district, Vietnam. Walking speed was assessed by a 4-Meter Walk Test with a usual-pace walking mode. Health-related characteristics of participants including risk of falls (The Timed Up and Go test, activities of daily living (ADL), instrumental activities of daily living (IADLs), cognitive impairment (Mini-Cog test) and frailty syndrome (The Reported Edmonton Frail Scale (REFS)). Multiple logistic regression was used to analyze the association between a slow walking speed and selected factors. A total of 364 older people were recruited, and the majority were female (65.4%). The overall average walking speed was 0.83 ± 0.27 m/s. The proportion of participants with a slow walking speed (

Background Alzheimer’s disease and related dementias (AD/ADRD) are a public health challenge for Vietnam because of its rapidly aging population. However, very few community-based programs exist to support people living with AD/ADRD and their family caregivers. Resources for Enhancing Alzheimer’s Caregiver Health in Vietnam (REACH VN) is a culturally adapted family caregiver intervention shown in a pilot study to be feasible and promising in terms of preliminary efficacy. We describe the protocol for a larger cluster randomized controlled trial (RCT) to test the efficacy of REACH VN among family caregivers of people living with dementia in a semi-rural area outside of Hanoi, Vietnam. Methods Thirty-two clusters with approximately 350 caregivers will be randomized to either REACH VN intervention or enhanced usual care. REACH VN is a multicomponent intervention delivered in-home or by phone over the course of 2 to 3 months. To be eligible, family caregivers need to be ≥18 years old, be the person who provides the most day-to-day care for people living with dementia, and have a score ≥ 6 on the Zarit Burden Interview-4. The primary outcomes are caregiver burden (Zarit Burden Interview-12) and psychological distress (Patient Health Questionnaire-4). Secondary outcomes include caregiver somatic symptoms (Patient Health Questionnaire-15) and perceived stress (Perceived Stress Scale-10). These outcomes will be assessed at baseline, 3 months, and 6 months. Exploratory analyses to examine potential mediators of primary outcomes are also planned. Discussion To our knowledge, this is the first large-scale study to test the efficacy of a community-based family dementia caregiver intervention in Vietnam. Results from this study will help inform efforts to widely deliver the REACH VN intervention or similar community-based family dementia caregiver support programs in Vietnam and other low- and middle-income countries (LMIC). Trial registration ClinicalTrials.govNCT04542317. Registered on 9 September 2020

5-FU is one of the key drugs in the treatment of gastric cancer (GC). Much evidence has shown that cancer stem cells (CSCs) play a key role in the acquisition of drug resistance. The organoid is a novel 3D cell culture system technology that sustains stem-cell-driven formation of near-physiological, self-renewing tissues using specific niche factors in a dish. In this study, we established GC organoids (GCOs) and gradually treated them with higher concentrations of 5-FU. We successfully harvested four 5-FU-resistant GCOs, which were supported by significant changes in the expression of molecules related to 5-FU metabolism. We then performed microarray analysis using three normal gastric organoids and three pairs of 5-FU-resistant and parental GCOs. Through the comparison of expression profiles and further validation, we chose KHDRBS3 as a target gene. We found KHDRBS3 to be an independent prognostic factor in GC patients, especially in GC patients treated with 5-FU chemotherapy. We also determined that KHDRBS3 might play an important role in the acquisition of stem cell-like features, such as multi-drug resistance and organoid formation, by regulating CD44 variant expression. We found KHDRBS3, which is thought to play an important role in the acquisition of characteristics of CSCs in GC, to be a promising candidate marker for predicting therapeutic effect and prognosis in GC patients.

The transcribed ultraconserved regions (T-UCRs) are a novel class of long non-coding RNAs and are involved in the development of several types of cancer. Although several different papers have described the oncogenic role of Uc.63+, there are no reports mentioning its importance in gastric cancer (GC) biology. In this study, we evaluated Uc.63+ expression using clinical samples of GC by qRT-PCR, and also assessed the correlation between Uc.63+ expression and clinico-pathological factors. The upregulation of Uc.63+ was significantly correlated with advanced clinico-pathological features. Knockdown of Uc.63+ significantly repressed GC cell growth and migration, whereas overexpression of Uc.63+ conversely promoted those of GC cells. In situ hybridization of Uc.63+ revealed its preferential expression in poorly differentiated adenocarcinoma. We further conducted a microarray analysis using MKN-1 cells overexpressing Uc.63- and found that NF-κB signaling was significantly upregulated in accordance with Uc.63+ expression. Our results suggest that Uc.63+ could be involved in GC progression by regulating GC cell growth and migration via NF-κB signaling

Background Bladder cancer (BC) is the 10th most common cancer in the world. BC with muscle invasion results in a poor prognosis and is usually fatal. Cancer cell metabolism has an essential role in the development and progression of tumors. Expression of tryptophan 2,3‐dioxygenase (TDO2) is associated with tumor progression and worse survival in some other cancers. However, no studies have been performed to uncover the biofunctional roles of TDO2 in BC. Aim This study aim to investigate the clinicopathologic significance of TDO2 in BC. Methods and results TDO2 expression was evaluated by qRT‐PCR and immunohistochemistry in an integrated analysis with the Cancer Genome Atlas (TCGA) and other published datasets. TDO2 overexpression was significantly associated with T classification, N classification, and M classification, tumor stage, recurrence, and basal type, and with the expression of CD44 and aldehyde dehydrogenase 1 (ALDH1) in BC. High TDO2 expression correlated with poor outcome of BC patients. Using BC cell lines with knockdown and forced expression of TDO2, we found that TDO2 was involved in the growth, migration, and invasiveness of BC cells. Moreover, TDO2 was found to be crucial for spheroid formation in BC cells. Importantly, TDO2 promoted BC cells resistance to cetuximab through integration of the EGFR pathway. Conclusion Our results indicate that TDO2 might take an essential part in BC progression and could be a potential marker for targeted therapy in BC.

The utility of Schlafen 11 (SLFN11) expression as a predictive biomarker for platinum-based chemotherapy has been established for cancers from different histologies. However, the therapeutic relevance of SLFN11 in bladder cancer (BC) is unknown. Here, we examined the clinicopathologic significance of SLFN11 expression across 120 BC cases by immunohistochemistry. We divided the cases into two cohorts, one including 50 patients who received adjuvant or neoadjuvant platinum-based chemotherapy, and the other including 70 BC patients treated by surgical resection without chemotherapy. In the cohort of 50 BC cases treated with platinum-based chemotherapy, the SLFN11-positive group (n = 25) showed significantly better overall survival than the SLFN11-negative group (n = 25, P = .012). Schlafen 11 expression correlated significantly with the expression of luminal subtype marker GATA3. Multivariate analyses identified SLFN11 expression as an independent prognostic predictor (odds ratio, 0.32; 95% confidence interval, 0.11-0.91; P = .033). Conversely, in the cohort of 70 BC cases not receiving platinum-based chemotherapy, the SLFN11-positive group (n = 29) showed significantly worse overall survival than the SLFN11-negative group (n = 41, P = .034). In vitro analyses using multiple BC cell lines confirmed that SLFN11 KO rendered cells resistant to cisplatin. The epigenetic modifying drugs 5-azacytidine and entinostat restored SLFN11 expression and resensitized cells to cisplatin and carboplatin in SLFN11-negative BC cell lines. We conclude that SLFN11 is a predictive biomarker for BC patients who undergo platinum-based chemotherapy and that the combination of epigenetic modifiers could rescue refractory BC patients to platinum derivatives by reactivating SLFN11 expression.

The interaction of chronic pain and depression among older people has been studied for many years. This study aimed to investigate the frequency of chronic pain and depression among older patients and correlated factors. A cross-sectional study was conducted in 921 older patients at the National Geriatric Hospital from November 2019 to March 2020. We used the Charlson Comorbidity Index (CCI) to assess the comorbid condition, a numerical rating scale (NRS) to examine pain severity, and Geriatric Depression Scale—15 items (GDS-15) to measure depression among participants. A chi-square test and Tobit regression were used to analyze the relationships. A total of 921 older patients participated in the study. The proportion of depression accounted for 55.8%. The mean Charlson score and number of diseases were 1.2 and 4.7, respectively. A positive correlation was found between comorbidity and chronic pain and depression. Moreover, socio-demographic variables such as occupation, education, and income were associated with pain and depressive symptoms. This study highlights the issue of mental health in older people with chronic pain. The results indicate the necessity of frequent depression screening, pain management, and social activity programs for older people to enhance their health.

Background Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme catabolizing tryptophan. Several lines of evidence revealed that overexpression of TDO2 is involved in anoikis resistance, spheroid formation, proliferation, and invasion and correlates with poor prognosis in some cancers. The aim of this research was to uncover the expression and biofunction of TDO2 in renal cell carcinoma (RCC). Methods To show the expression of TDO2 in RCC, we performed qRT-PCR and immunohistochemistry in integration with TCGA data analysis. The interaction of TDO2 with PD-L1, CD44, PTEN, and TDO2 expression was evaluated. We explored proliferation, colony formation, and invasion in RCC cells line affected by knockdown of TDO2. Results RNA-Seq and immunohistochemical analysis showed that TDO2 expression was upregulated in RCC tissues and was associated with advanced disease and poor survival of RCC patients. Furthermore, TDO2 was co-expressed with PD-L1 and CD44. In silico analysis and in vitro knockout of PTEN in RCC cell lines revealed the ability of PTEN to regulate the expression of TDO2. Knockdown of TDO2 suppressed the proliferation and invasion of RCC cells. Conclusion Our results suggest that TDO2 might have an important role in disease progression and could be a promising marker for targeted therapy in RCC. (199 words)

Although docetaxel (DTX) confers significant survival benefits in patients with castration‐resistant prostate cancer (CRPC), resistance to DTX inevitably occurs. Therefore, clarifying the mechanisms of DTX resistance may improve survival in patients with CRPC. Claspin plays a pivotal role in DNA replication stress and damage responses and is an essential regulator for the S‐phase checkpoint. CLSPN is an oncogenic gene that contributes to tumor proliferation in several human solid tumors. However, the clinical significance of claspin in prostate cancer (PCa) has not been examined. The present study aimed to elucidate the role of claspin and its relationship with DTX resistance in PCa. We immunohistochemically analyzed the expression of claspin in 89 PCa cases, of which 31 (35%) were positive for claspin. Claspin‐positive cases were associated with higher Gleason score, venous invasion, and perineural invasion. Kaplan–Meier analysis showed that high claspin expression was related to poor prostate‐specific antigen (PSA) relapse‐free prognosis. In a public database, high CLSPN expression was associated with poor PSA relapse‐free prognosis, Gleason score, T stage, lymph node metastasis, CRPC, and metastatic PCa. Claspin knockdown by siRNA decreased cell proliferation, upregulated DTX sensitivity, and suppressed the expression of Akt, Erk1/2, and CHK1 phosphorylation in DU145 and PC3 cell lines. Furthermore, claspin expression was much more upregulated in DTX‐resistant DU145 (DU145‐DR) than in parental DU145 cells. Claspin knockdown significantly upregulated the sensitivity to DTX in DU145‐DR cells. These results suggest that claspin plays an important role in PCa tumor progression and DTX resistance., Claspin overexpression was related to poor PSA relapse‐free prognosis. Claspin knockdown significantly upregulated the sensitivity to docetaxel in DU145 docetaxel‐resistant cells.

Falls in older people are a major public health issue, as they are associated with increased risks of morbidity and mortality. This study aims to investigate the prevalence and factors associated with falls among older outpatients. A cross-sectional study was conducted in 539 outpatients aged 60 and over at the National Geriatric Hospital, Hanoi, Vietnam. Falls and their associated factors were analyzed by multivariable logistic regression. The prevalence of falls was 23.7% (single fall 17.9%, recurrent falls 5.8%). The majority of falls occurred at home (69.6%) and were caused by a slippery floor (51.6%). After falling, most patients sustained physical injuries (65.6%), notably, women suffered more severe injuries than men. Alcohol consumption, using psychotropic medications, having three or more comorbidities, hypertension, COPD, urinary incontinence, frailty, fear of falling, ADL/IADL limitation, slow walking speed and mobility impairment were significantly associated with falls. Overall, the data indicated that falls were prevalent among older outpatients. Behavior factors, comorbidities, geriatric syndromes and physical function were substantially associated with falls, suggesting that most falls are preventable. Further longitudinal studies of longer periods are needed to comprehensively investigate the risk factors for falls.

Objective. To describe handgrip strength (HGS) and identify associated factors in community-dwelling older adults in rural Vietnam. Methods. A cross-sectional study was conducted in community-dwelling older adults 80 years and over in five rural communities in Hanoi, Vietnam. Age-gender-BMI stratified HGS values were reported as means and standard deviations. Demographic characteristics, malnutrition, risk of fall, basic activities of daily living (ADL), and instrumental activities of daily living (IADL) were investigated. Multivariate linear regression explored the association between HGS and these factors. Results. In 308 participants, mean age was 85.4 ± 4.2 years. Mean HGS was 21.6 ± 6.1 kg for males and 15.3 ± 4.3 kg for females. HGS in our sample was generally lower than that in other European countries and Asian threshold. Low HGS was correlated with older age ( β = − 0.196 , p < 0.001 ), female ( β = − 0.443 , p < 0.001 ), low education ( β = − 0.130 , p < 0.05 ), risk of falls ( β = − 0.114 , p < 0.05 ), and lower IADL ( β = 0.153 , p = 0.001 ). Conclusions. The age-gender-BMI stratified HGS values of 80 years and over community-dwellers in rural Vietnam were described. HGS decreased with advanced age, female, low education, high risk of falls, and impaired IADLs. The results could provide useful reference data for further investigations and measures in clinical practice.

Objectives. This study investigated associations between frailty and functional disability in elder suburban Vietnamese. Method. Cross-sectional analysis was carried out on 251 participants aged 80 and over in Soc Son district. We used the Instrumental Activities of Daily Living (IADL) scale including 8 items, and functional disability was defined as ≥3 IADL impairment. We defined frail as ≥3 out of 5 frailty components including weight loss > 5 % , weak grip, exhaustion, low walking speed, and low physical activity. Results. Of 251 participants with a mean age of 84.6, 11.2% was classified as frail and 64.5% had ≥3 IADLs. Among the frailty components, low walking speed and low physical activity were significantly associated with increased odds of having ≥3 IADLs: ORs (95% CI) were 4.2 (2.3-7.9) and 3.7 (1.7-8.2). Conclusion. Frailty is associated with the higher likelihood of having functional disability. Further longitudinal studies are needed to examine the causal this relationship.

ObjectivesThis study aims to investigate the prevalence of sarcopenia and its associated factors in patients attending geriatric clinics in Vietnam.Design and settingA cross-sectional study was conducted in consecutive patients aged ≥60 visiting outpatient clinics of the National Geriatric Hospital in Hanoi, Vietnam, from January 2018 to October 2018. Handgrip strength was measured with a hand dynamometer. Whole-body dual-energy X-ray absorptiometry was applied to measure the appendicular skeletal muscle mass. Sarcopenia was defined by the criteria proposed by the Asian Working Group for Sarcopenia (AWGS 2019) and by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project.ResultsThere were 600 participants, mean age 70.0±8.0, 60.8% female. The prevalence of sarcopenia was 54.7% according to AWGS 2019 criteria and 40.5% according to FNIH. In multivariate logistic regression, age (adjusted OR 1.08, 95% CI 1.05 to 1.11), male (adjusted OR 2.03, 95% CI 1.29 to 3.21), underweight (adjusted OR 2.32, 95% CI 1.22 to 4.41), being malnourished (adjusted OR 3.77, 95% CI 1.19 to 11.91), chronic lung diseases (adjusted OR 3.48, 95% CI 2.10 to 5.77) and lower physical activity were significantly associated with sarcopenia defined by AWGS 2019 criteria. With FNIH definition, the significantly associated factors were age (adjusted OR 1.07, 95% CI 1.04 to 1.11), male (adjusted OR 6.78, 95% CI 4.12 to 11.17), low education (adjusted OR 2.15, 95% CI 1.27 to 3.63), being malnourished (adjusted OR 3.35, 95% CI 1.28 to 8.76), chronic lung diseases (adjusted OR 2.58, 95% CI 1.56 to 4.28) and lower physical activity level.ConclusionThe prevalence of sarcopenia in patients attending geriatric clinics was high. Further studies are needed to examine the impact of sarcopenia on adverse outcomes in this population.

Deoxycholic acid (DCA), a secondary bile acid, is reportedly increased in the serum of patients with nonalcoholic steatohepatitis and animals with experimentally induced hepatocellular carcinoma (HCC), but its contribution to malignant behaviors of HCC has not been precisely clarified. This study aimed to examine the effect of DCA on hepatic stellate cells (HSCs), a major component of nonparenchymal cells in the liver, and its subsequent indirect effect on HCC cells.LX2 cells, a human HSC line, were treated with DCA in vitro. Then, HuH7 cells, a human hepatoma cell line, were incubated in conditioned media of DCA-treated LX2 to investigate the subsequent effect focusing on malignant behaviors.DCA resulted in cellular senescence in LX2 with the decreased cell proliferation via cell cycle arrest at G0/1 phase, together with the induction of senescence-associated secretory phenotype (SASP) factors. To investigate the influence of SASP factors secreted by HSCs in response to DCA, HCC cells were treated with conditioned media that promoted cell migration and invasion via induction of epithelial mesenchymal transition. These changes were attenuated in the presence of neutralizing antibody against IL8 or TGFβ. Pathological analysis of surgical specimens from HCC patients revealed that senescent HSCs were detected in the stroma surrounding HCC.Our data suggest an important role of HSC senescence caused by DCA for the malignant biological behaviors of HCC via induction of SASP factors, particularly IL8 and TGFβ.

Cancer is the second leading cause of death globally, and despite the advances in drug development, it is still necessary to develop new plant-derived medicines. Compared with using conventional chemical drugs to decrease the side effects induced by chemotherapy, natural herbal medicines have many advantages. The present study aimed to discover the potential cytotoxicity of ethanol extract and its derived fractions (chloroform, ethyl acetate, butanol, and aqueous) of Adenosma bracteosum Bonati. (A. bracteosum) on human large cell lung carcinoma (NCI-H460) and hepatocellular carcinoma (HepG2). Among these fractions, the chloroform showed significant activity in the inhibition of proliferation of both cancerous cells because of the presence of bioactive compounds including xanthomicrol, 5,4’-dihydroxy-6,7,8,3’-tetramethoxyflavone, and ursolic acid which were clearly revealed by nuclear magnetic resonance spectroscopy (1H-NMR, 13C-NMR, Heteronuclear Multiple Bond Coherence, and Heteronuclear Single Quantum Coherence Spectroscopy) analyses. According to the radical scavenging capacity, the 5,4’-dihydroxy-6,7,8,3’-tetramethoxyflavone compound (AB2) exhibited the highest anticancer activity on both NCI-H460 and HepG2 with IC50 values of 4.57 ± 0.32 and 5.67 ± 0.09 µg/mL respectively, followed by the ursolic acid with the lower percent inhibition at 13.05 ± 0.55 and 10.00 ± 0.16 µg/mL, respectively (p < 0.05). Remarkably, the AB2 compound induced to significant increase in the production of reactive oxygen species accompanied by attenuation of mitochondrial membrane potential, thus inducing the activation of caspase-3 activity in both human lung and liver cancer cells. These results suggest that A. bracteosum is a promising source of useful natural products and AB2 offers opportunities to develop the novel anticancer drugs.

Background The SARC-F questionnaire has been developed as a rapid diagnostic test that can be used to screen for sarcopenia. Aim To investigate the reliability and validity of the Vietnamese version of SARC-F as a screening tool for sarcopenia in older patients in Vietnam. Methods A cross-sectional study was conducted in older people attending the outpatient clinics of the National Geriatric Hospital in Vietnam. Muscle mass (using dual-energy X-ray absorptiometry), handgrip strength and gait speed were assessed. SARC-F was validated against the three standard criteria for sarcopenia: the Foundation for the National Institutes of Health (FNIH), Asia Working Group for Sarcopenia (AWGS 2019) and European Working Group on Sarcopenia in Older People (EWGSOP2). Results There were 764 participants (mean age 71.5 ± 8.9 years). The Vietnamese SARC-F questionnaire had a good internal consistency (Cronbach’s alpha 0.85). The prevalence of sarcopenia was 49.2% according to SARC-F and 48.3%, 61.1% and 52.6% according to FNIH, AWGS 2019 and EWGSOP2, respectively. The sensitivity and specificity of SARC-F in identifying sarcopenia were 67.1% and 66.7% (for FINH), 66.7% and 67.1% (for AWGS 2019), and 64.9% and 68.2% (for EWGSOP2). The AUCs of SARC-F were 0.71–0.72 against the three sarcopenia criteria. Conclusion The Vietnamese version of SARC-F questionnaire has acceptable diagnostic value for sarcopenia. SARC-F could be used as an initial screening for sarcopenia in hospital clinics.

Objective: To foster a national dialogue on addressing dementia as an emerging public health problem and formulating a strategy for developing Vietnam's national dementia plan. Methods: In September 2018, the Vietnamese National Geriatric Hospital supported by University staff in Australia and the United States organised the first Vietnam National Dementia Conference in Hanoi. Results: Over 270 Vietnamese dementia stakeholders and international dementia experts participated in the conference. The participants agreed dementia was a public health priority in Vietnam and identified the need for the development of Vietnam's national dementia plan. Policymakers supported positioning dementia as a priority in the national health agenda. Research institutions created collaboration to generate scientific information for policymaking process. Funding and international supports were obtained to develop Vietnam's national dementia plan. Conclusion: Strong leadership, stakeholder engagement and international support are critical in raising awareness and advocating for the development of Vietnam's national dementia plan usc Refereed/Peer-reviewed

Objective: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. Methods: TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). Results: TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. Conclusion: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.

This study assessed the knowledge and attitude toward palliative care for the elderly among health professionals in a tertiary geriatric hospital in Vietnam and explored their determinants. Cross-sectional data were obtained on 161 geriatric health professionals at the National Geriatric Hospital. Modified-Palliative Care Knowledge Test and Frommelt Attitudes Toward Care of the Dying instruments were used to measure knowledge and attitude toward geriatric palliative care. As a result, 40.5% physicians and 74.2% nurses showed insufficient knowledge about geriatric palliative care (p &lt, 0.05). The lowest score was for dyspnea, following by gastrointestinal and pain problems. No significant difference was found regarding the attitude between physicians and nurses (p &gt, 0.05). Health professional category, age, and years of experience were found to be associated with knowledge about palliative care. Meanwhile, only knowledge score had correlations with total attitude score (Coef. = 0.2, 95%CI = 0.1&ndash, 0.3), attitude toward patients (Coef. = 0.1, 95%CI = 0.0&ndash, 0.1) and toward patients&rsquo, family (Coef. = 0.1, 0.1). This study highlights a significant knowledge gap and preferable attitude toward palliative care for the elderly among physicians and nurses in the geriatric hospital. Intensive training about geriatric palliative care, focusing on pain, dyspnea and gastrointestinal issue management, should be performed to ensure the quality of palliative care services, especially in nurses.

Objectives To investigate the prevalence of polypharmacy and the common drugs prescribed at discharge in frail and non-frail older inpatients, and to examine whether frailty is significantly associated with polypharmacy. Methods Cross-sectional analysis from data of a study about the prevalence of frailty in older inpatients in Vietnam in 2015. Polypharmacy was defined as using ≥5 medications. Frailty was defined by Fried's frailty criteria. Results There were 382 participants, mean age 76.4, 56.5% female and 35.9% frail. At discharge, 59.2% had polypharmacy (62.8% in the frail and 57.1% in the non-frail). Vitamin/supplements were the most common drugs prescribed, followed by antiplatelets. Frailty was not significantly associated with polypharmacy (adjusted OR 1.45, 95% CI 0.89-2.34). Conclusions The prevalence of polypharmacy at discharge was high in both frail and non-frail participants. The association between frailty and polypharmacy needs to be investigated further in multicentre studies with larger sample sizes in Vietnam.

Two new prenylated flavonoids, 4´-methyl-8-prenyltaxifolin (

Anh Trung Nguyen,1,2 Thanh Xuan Nguyen,1,2 Tu N Nguyen,1,3 Thu Hoai Thi Nguyen,1,2,4 Thang Pham,1,2 Robert Cumming,5 Sarah N Hilmer,6 Huyen Thi Thanh Vu1,2 1The National Geriatric Hospital, Hanoi, Vietnam; 2Department of Geriatrics and Gerontology, Hanoi Medical University, Hanoi, Vietnam; 3Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; 4Dinh Tien Hoang Institute of Medicine, Hanoi, Vietnam; 5Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; 6Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital and Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia Aims: To investigate the impact of frailty on outcomes in older hospitalized patients, including prolonged length of stay and all-cause mortality 6 months after admission, using both the frailty phenotype and the Reported Edmonton Frail Scale (REFS).Patients and methods: This study is the follow-up phase of a study designed to investigate the prevalence of frailty and its impact on adverse outcomes in older hospitalized patients at the National Geriatric Hospital in Hanoi, Vietnam.Results: A total of 461 participants were included, with a mean age 76.2±8.9 years, and 56.8% were female. The prevalence of frailty was 31.9% according to the REFS and 35.4% according to Fried’s criteria. The kappa coefficient was 0.57 (95% CI =0.49–0.66) between the two frailty criteria in identifying frail and non-frail participants. There was a trend toward increasing the likelihood of prolonged hospitalization in participants with frailty defined by Fried’s criteria (adjusted OR =1.49, 95%CI =0.94–2.35) or by REFS (adjusted OR =1.43, 95% CI =0.89–2.29). During 6 months of follow-up, 210 were lost and 18/251 (7.2%) participants died. Mortality was higher in those with frailty defined by either Fried’s criteria or REFS. On multivariable survival analysis, adjusted HRs for mortality were 2.65 (95% CI =1.02–6.89) for Fried’s criteria and 4.19 (95% CI =1.59–10.99) for REFS.Conclusion: Fried’s frailty phenotype or REFS can be used as a screening tool to detect frailty in older inpatients in Vietnam and predict mortality. Frailty screening can help prioritize targeted frailty-tailored treatments, such as nutrition, early mobility and medication review, for these vulnerable patients to improve clinical outcomes. Keywords: frailty, elderly, inpatients, Vietnam

Background The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. Methods Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A. Results qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1. Conclusions The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target. Electronic supplementary material The online version of this article (10.1186/s12885-018-4863-y) contains supplementary material, which is available to authorized users.

This study examined the use of potentially inappropriate medicines that may affect cognition (PIMcog) in people with dementia and its associated factors. Medical records of all outpatients with dementia attending a tertiary hospital in Vietnam between January 1, 2015, and December 31, 2016, were examined. Medicine use was assessed against a list of PIMcog. Variables associated with having a PIMcog were assessed using a multiple logistic regression. Of the 128 patients, 41% used a PIMcog, 39.1% used cholinesterase inhibitors (CEIs) concomitantly with anticholinergics, and 18% used antipsychotics. The number of hospital visits (adjusted odds ratio [OR]: 1.08; 95% confidence interval [CI]: 1.02-1.16) and number of treating specialists (adjusted OR: 0.61; 95% CI: 0.45-0.83) were associated with PIMcog use. This study highlights a high-level use of medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia. Efforts to improve quality use of medicines for this population are warranted. Refereed/Peer-reviewed

Introduction : In Vietnam, HIV testing services had been available only at provincial and district health facilities, but not at the primary health facilities. Consequently, access to HIV testing services had been limited especially in rural areas. In 2012, Vietnam piloted decentralization and integration of HIV services at commune health stations (CHSs). As a part of this pilot, a three-rapid test algorithm was introduced at CHSs. The objective of this study was to assess the performance of a three-rapid test algorithm and the implementation of quality assurance measures to prevent misdiagnosis, at primary health facilities. Methods : The three-rapid test algorithm (Determine HIV-1/2, followed by ACON HIV 1/2 and DoubleCheckGold HIV 1&2 in parallel) was piloted at CHSs from August 2012 to December 2013. Commune health staff were trained to perform HIV testing. Specimens from CHSs were sent to the provincial confirmatory laboratory (PCL) for confirmatory and validation testing. Quality assurance measures were undertaken including training, competency assessment, field technical assistance, supervision and monitoring and external quality assessment (EQA). Data on HIV testing were collected from the testing logbooks at commune and provincial facilities. Descriptive analysis was conducted. Sensitivity and specificity of the rapid testing algorithm were calculated. Results : A total of 1,373 people received HIV testing and counselling (HTC) at CHSs. Eighty people were diagnosed with HIV infection (5.8%). The 755/1244 specimens reported as HIV negative at the CHS were sent to PCL and confirmed as negative, and all 80 specimens reported as HIV positive at CHS were confirmed as positive at the PCL. Forty-nine specimens that were reactive with Determine but negative with ACON and DoubleCheckGold at the CHSs were confirmed negative at the PCL. The results show this rapid test algorithm to be 100% sensitive and 100% specific. Of 21 CHSs that received two rounds of EQA panels, 20 CHSs submitted accurate results. Conclusions : Decentralization of HIV confirmatory testing to CHS is feasible in Vietnam. The results obtained from this pilot provided strong evidence of the feasibility of HIV testing at primary health facilities. Quality assurance measures including training, competency assessment, regular monitoring and supervision and an EQA scheme are essential for prevention of misdiagnosis. Keywords HIV testing; rapid test; algorithm; decentralization; misdiagnosis; quality assurance; Vietnam (Published: 29 August 2017) Nguyen VTT et al. Journal of the International AIDS Society 2017, 20 :21752 http://www.jiasociety.org/index.php/jias/article/view/21752 | http://dx.doi.org/10.7448/IAS.20.7.21752

Background Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. Materials and methods BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. Results Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. Conclusion These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC.

Measuring health-related quality of life (HRQOL) is critical to evaluate the burden of frailty in the older population.This study explored the prevalence of frailty among Vietnamese older people in rural communities, determined the factors associated with frailty, and examined the differences in HRQOL between non-frail, pre-frail, and frail people. A cross-sectional study was conducted on older adults (&ge, 60 years old) residing in Soc Son district, northern Vietnam. Non-frailty, pre-frailty, and frailty conditions were evaluated using Fried&rsquo, s frailty criteria. The EuroQol-5 Dimensions-5 Levels(EQ-5D-5L) instrument was employed to measure HRQOL. Socioeconomic, behavioral, health status, and healthcare utilization characteristics were collected as covariates. Among 523 older adults, 65.6% were pre-frail, and 21.7% were frail. The mean EQ-5D-5L indexes of the non-frailty, pre-frailty, and frailty groups were 0.70 (SD = 0.18), 0.70 (SD = 0.19), and 0.58 (SD = 0.20), respectively. The differences were found between non-frailty and frailty groups (p &lt, 0.01), as well as the pre-frailty and frailty groups (p&lt, 0.01). After adjusting for covariates, the estimated mean difference in the HRQOL between the non-frailty and frailty groups was &minus, 0.10 (95%CI= &minus, 0.17, &minus, 0.02) (R2 = 45.2%), showing a 10% reduction of the maximum EQ-5D-5L index.This study emphasized the high prevalence of frailty among older adults in the rural communities of Vietnam. Frailty was found to be associated with a small reduction of HRQOL in this population.

(1) Background: Major causes of the burden of disease in older persons include mental disorders and neurological diseases, such as depression. This study aims to explore the prevalence of older people at risk for depression and identify the factors associated with this risk in rural Vietnam. (2) Methods: A cross-sectional study was conducted in Soc Son, Hanoi with 523 community dwelling elders aged 60 and over. Face-to-face interviews were performed to collect data about socioeconomic status, risk for depression, health status, and health utilization. The Geriatric Depression Scale-4 items (GDS-4) was used to assess the risk for depression occurrence. Multivariable logistic regression was employed for determining the factors associated with the risk for depression. (3) Results: Among 523 participants, there were 26.4% of participants at risk for depression. The proportion of females at risk for depression (29.0%) was significantly higher than males (20.4%). Differences were found in economic status (near poor group had higher risk for depression compared to the poor group) (p &lt, 0.01). Older adults living with spouse/partner, living in near-poor household, and suffering pain/discomfort were all more likely to be at risk for depression. (4) Conclusions: Being female, living in a near poor household, being in pain or experiencing discomfort are all factors strongly correlated to high risk for depression. These findings highlight the urgent need for additional research among Vietnamese community-dwelling older people.

In Vietnam, as in much of the world, the elderly population is growing rapidly. Two-thirds of Vietnam&rsquo, s elderly live in rural areas, where there may be unique health profiles and needs. Furthermore, the sex ratio in the elderly population is highly skewed. The relationship between sex, health-seeking behavior, and health outcomes in elderly individuals residing in rural areas has not been well-characterized, and needs to be elucidated in order to better serve this population. This study sought to explore the associations of sex with health and health-seeking behavior among the elderly in Soc Son, a rural district of Hanoi. A cross-sectional design was employed, elderly women and men were surveyed across the domains of socioeconomic information, health status, and healthcare service utilization. We found differences between women and men in sociodemographic characteristics, quality of life, health outcomes, and patterns of health services utilization. Overall, women had poorer health and quality of life, but no difference was found between sexes regarding level of health services utilization. Future research should expand upon these findings and, moreover, characterize their underlying systemic, sociocultural, and psychological mechanisms, in order to help bring solutions to improve the health of elderly persons in rural parts of Vietnam.

A gene-level targeted enrichment method for direct detection of epigenetic modifications is described. The approach is demonstrated on the CGG-repeat region of the FMR1 gene, for which large repeat expansions, hitherto refractory to sequencing, are known to cause fragile X syndrome. In addition to achieving a single-locus enrichment of nearly 700,000-fold, the elimination of all amplification steps removes PCR-induced bias in the repeat count and preserves the native epigenetic modifications of the DNA. In conjunction with the single-molecule real-time sequencing approach, this enrichment method enables direct readout of the methylation status and the CGG repeat number of the FMR1 allele(s) for a clonally derived cell line. The current method avoids potential biases introduced through chemical modification and/or amplification methods for indirect detection of CpG methylation events.

Surveying 60 Vietnamese patients with either current or past post-traumatic stress disorder, this article aims to phenomenologically characterize the syndrome of `hit by the wind' in a multidimensional manner. This includes determining the patient conceptualization of the disorder, profiling `hit by the wind' episodes suffered by patients in the previous month, and presenting case vignettes. Eighteen of the 60 patients (30%) suffered at least one episode of `hit by the wind' in the last month; all 18 patients had at least one episode of `hit by the wind' in the last month that met panic attack criteria. For the 18 patients, 33 episodes of `hit by the wind' that met panic attack criteria were experienced in the previous month. For these 33 episodes, the most frequently reported DSM-IV panic attack symptoms were chills (100%; 33/33) and dizziness (88%; 29/33). Flashbacks played a role in the `hit by the wind' episodes for 5 of the 18 patients (28%). In the discussion, a model of how the syndrome of `hit by the wind' generates panic is adduced; also, possible Chinese origins of the disorder are discussed.

It has been known since 1986 that CD8 T lymphocytes from certain HIV-1-infected individuals who are immunologically stable secrete a soluble factor, termed CAF, that suppresses HIV-1 replication. However, the identity of CAF remained elusive despite an extensive search. By means of a protein-chip technology, we identified a cluster of proteins that were secreted when CD8 T cells from long-term nonprogressors with HIV-1 infection were stimulated. These proteins were identified as alpha-defensin 1, 2, and 3 on the basis of specific antibody recognition and amino acid sequencing. CAF activity was eliminated or neutralized by an antibody specific for human alpha-defensins. Synthetic and purified preparations of alpha-defensins also inhibited the replication of HIV-1 isolates in vitro. Taken together, our results indicate that alpha-defensin 1, 2, and 3 collectively account for much of the anti-HIV-1 activity of CAF that is not attributable to beta-chemokines.

This study surveys Vietnamese refugees attending two psychiatric clinics to determine both the prevalence of panic disorder (PD) as well as panic attack subtypes in those suffering PD. A culturally valid adaptation of the SCID-panic module (the Vietnamese Panic Disorder Survey or VPDS) was administered to 100 Vietnamese refugees attending two psychiatric clinics. Utilizing culturally sensitive panic probes, the VPDS provides information regarding both the presence of PD and panic attack subtypes during the month prior to interview. Of 100 patients surveyed, 50 (50%) currently suffered PD. Among the 50 patients suffering PD, the most common panic attack subtypes during the previous month were the following: "orthostatic dizziness" (74% of the 50 panic disorder patients [PDPs]), headache (50% of PDPs), wind-induced/temperature-shift-induced (24% of PDPs), effort-induced (18% of PDPs), gastro-intestinal (16% of PDPs), micturition-induced (8% of PDPs), out-of-the-blue palpitations (24% of PDPs), and out-of-the-blue shortness of breath (16% of PDPs). Five mechanisms are adduced to account for this high PD prevalence as well as the specific profile of subtypes: 1) a trauma-caused panic attack diathesis; 2) trauma-event cues; 3) ethnic differences in physiology; 4) catastrophic cognitions generated by cultural syndromes; and 5) a modification of Clark's spiral of panic.

The purpose of this study was to determine in Vietnamese ex-political detainees newly arrived into the United States a) the prevalence of torture and psychiatric symptoms and b) the dose-effect relationships between cumulative torture experience and the psychiatric symptoms of posttraumatic stress disorder (PTSD) and major depression. The study population included Vietnamese ex-political detainees (N = 51) and a comparison group (N = 22). All respondents received culturally validated instruments with known psychometric properties including Vietnamese versions of the Hopkins Symptom Checklist-25 and the Harvard Trauma Questionnaire. The ex-political detainees, in contrast to the comparison group, had experienced more torture events (12.2 SD = 4.2 vs. 2.6 SD = 3.1) and had higher rates of PTSD (90% vs. 79%) and depression (49% vs. 15%). Dose-effect relationships between cumulative torture experience and psychiatric symptoms were positive with the PTSD subcategory of "increased arousal" revealing the strongest association. These findings provide evidence that torture is associated with psychiatric morbidity in Vietnamese refugees. The demonstration of significant dose-effect responses supports the hypothesis that torture is a major risk factor in the etiology of major depression and PTSD. The generalizability of these results to other torture survivor groups is unknown. The interaction between torture and other pre- and post-migration risk factors over time in different cultural settings still needs to be examined.

Interleukin-7 (IL-7) concentrations are increased in the blood of CD4+ T cell depleted individuals, including HIV-1 infected patients. High IL-7 levels might stimulate T cell activation and, as we have shown earlier, IL-7 can prime resting T cell to CD95 induced apoptosis as well. HIV-1 infection leads to B cell abnormalities including increased apoptosis via the CD95 (Fas) death receptor pathway and loss of memory B cells. Peripheral B cells are not sensitive for IL-7, due to the lack of IL-7Ra expression on their surface; however, here we demonstrate that high IL-7 concentration can prime resting B cells to CD95-mediated apoptosis via an indirect mechanism. T cells cultured with IL-7 induced high CD95 expression on resting B cells together with an increased sensitivity to CD95 mediated apoptosis. As the mediator molecule responsible for B cell priming to CD95 mediated apoptosis we identified the cytokine IFN-γ that T cells secreted in high amounts in response to IL-7. These results suggest that the lymphopenia induced cytokine IL-7 can contribute to the increased B cell apoptosis observed in HIV-1 infected individuals.

Context.—Current tumor markers for ovarian cancer still lack adequate sensitivity and specificity to be applicable in large populations. High-throughput proteomic profiling and bioinformatics tools allow for the rapid screening of a large number of potential biomarkers in serum, plasma, or other body fluids. Objective.—To determine whether protein profiles of plasma can be used to identify potential biomarkers that improve the detection of ovarian cancer. Design.—We analyzed plasma samples that had been collected between 1998 and 2001 from patients with sporadic ovarian serous neoplasms before tumor resection at various International Federation of Gynecology and Obstetrics stages (stage I [n = 11], stage II [n = 3], and stage III [n = 29]) and from women without known neoplastic disease (n = 38) using proteomic profiling and bioinformatics. We compared results between the patients with and without cancer and evaluated their discriminatory performance against that of the cancer antigen 125 (CA125) tumor marker. Results.—We selected 7 biomarkers based on their collective contribution to the separation of the 2 patient groups. Among them, we further purified and subsequently identified 3 biomarkers. Individually, the biomarkers did not perform better than CA125. However, a combination of 4 of the biomarkers significantly improved performance (P ≤ .001). The new biomarkers were complementary to CA125. At a fixed specificity of 94%, an index combining 2 of the biomarkers and CA125 achieves a sensitivity of 94% (95% confidence interval, 85%–100.0%) in contrast to a sensitivity of 81% (95% confidence interval, 68%–95%) for CA125 alone. Conclusions.—The combined use of bioinformatics tools and proteomic profiling provides an effective approach to screen for potential tumor markers. Comparison of plasma profiles from patients with and without known ovarian cancer uncovered a panel of potential biomarkers for detection of ovarian cancer with discriminatory power complementary to that of CA125. Additional studies are required to further validate these biomarkers.

The insulin receptor gene is induced 8 to 10-fold during adipocyte differentiation. Plasmids containing the promoter, exon 1 and a portion of the first intron from either the mouse or human gene are able to modulate the expression of an insulin receptor/CAT gene 3 to 7-fold during differentiation. We have shown that several nuclear proteins from both preadipocyte and adipocyte nuclear extracts bind to two discrete sites within a 278-bp region in the 5′ end of the first intron. Sequence comparison between the first intron of the human gene and the mouse gene shows two regions of sequence identity which correspond to the protein binding regions detected by DNase footprinting. One of these sites binds proteins that are enriched in adipocyte nuclear extracts and can be competed by adipose regulatory element, ARE6.

The aim of this study was to investigate the validity of the Harvard Trauma Questionnaire (HTQ) and the depression sub-scale of the Hopkins Symptom Checklist-25 (HSCL-25) in screening for post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) among Vietnamese former political prisoners (POWs). The study population included Vietnamese POWs (n = 51) who migrated to the Boston metropolitan area between January 1990 and July 1992 under the Special Released Re-education Center Detainees Resettlement Program. The criterion validity of the HTQ in assessing PTSD and of the depression sub-scale of the HSCL-25 in assessing MDD is supported by the results. Consideration of an appropriate cut-off score should include examination of the utility of a given screening instrument for PTSD or MDD within different settings, such as refugee camps vs. countries of third asylum.

Within human insulin receptor gene there are three consensus binding sites for the CAAT/enhancer binding protein (C/EBP). Two sites are located in the 5′ flanking region and the other is in the first intron. We have studied the ability of these sequences to be regulated by C/EBP. A eukaryotic expression vector containing these sequences can be transactivated in a dose-dependent manner by a C/EBP expression vector when co-transfected into NIH-3T3 cells. In addition, double stranded oligonucleotides corresponding to two of these sequences can bind C/EBP in a gel retardation assay. These two oligonucleotides can compete with each other to bind C/EBP. These findings suggest that this transcription factor may play a role in the regulation of insulin receptor gene expression in vivo .

The insulin receptor plays a critical role in the maintenance of glucose homeostasis. Regulation of this key function must be under stringent controls. In order to study the regulation of insulin receptor gene expression, we have cloned, sequenced and characterized its promoter. The first exon of the insulin receptor gene is embedded in an unusual segment of DNA composed of Alu repeats. The promoter has the characteristics typical of a housekeeping gene. It is GC-rich and has multiple start sites of transcription. A 574 base pair fragment immediately upstream of the translation initiation site contains promoter activity when transfected into eukaryotic cell lines. Deletion analysis was performed to study promoter function. These studies showed that only 150 base pairs of promoter sequence were necessary for promoter function. This region contains three potential binding sites for the transcription factor, Sp1 and a TC box sequence. Furthermore, the fragment functions equally well in either orientation. We have defined an element in this region with enhancer function for both its homologous and a heterologous promoter. In addition, this region seems to contribute some degree of tissue specificity to insulin receptor gene expression.