Gastrointestinal parasitosis in cattle: Unveiling the landscape across diverse production systems in Bangladesh.

BACKGROUND: Factors influencing parasitosis in cattle in Bangladesh remain inadequately explored, necessitating a comprehensive investigation for interventions and sustainable livestock farming. OBJECTIVES: We conducted this study to estimate the prevalence and distribution of gastrointestinal parasites, exploring their intricate relationship with farm management practices across a spectrum of small-, medium-, and large-scale commercial farms. METHODS: We conducted this study in the Chattogram district of Bangladesh. We collected a total of 189 freshly voided faecal samples from different farms. We recorded the age, breed, milking status, sex, body condition score, and anthelmintic use history of the sampled animals. We processed the samples using the direct smear method, with the identification of one egg per sample being considered positive. RESULTS: We estimated the prevalence of gastrointestinal parasite infection in large-scale (52.1%), medium-scale (54.5%), and small-scale farms (70.0%), with statistically significant differences (p ≤ 0.05). Both pregnant and lactating cows, as well as indigenous cattle, were more likely to have gastrointestinal parasites (p ≤ 0.05). The predominant parasites across farms of all sizes were trematodes (Paramphistomum spp. and Schistosomas spp.) and protozoa (Balantidium coli and Coccidia spp.). CONCLUSION: Poor farm management practices, such as no pasture management and inadequate deworming regimens, may contribute to the elevated prevalence and infection load observed on small-scale farms. The increased parasitosis in previously dewormed animals can be attributed to the development of anthelmintic resistance against gastrointestinal parasites. Implementing proper and effective deworming strategies is crucial to preventing gastrointestinal parasitosis and mitigating the risk of anthelmintic resistance.

Identifying Benefits, Challenges, and Options for Improvement of Veterinary Work-Based Learning in Bangladesh.

Work-based learning (WBL) provides relevant contemporary experience of working environments. Potential benefits for students include developing invaluable skills (clinical, personal, cultural, and professional) and gaining greater awareness of the profession and future career opportunities. However, there are also challenges related to running and sustaining a successful WBL program. In the context of this study, WBL refers to external placements undertaken by final-year students. The aims of the study were to identify ways to optimize the benefits while managing the challenges in delivering WBL in a veterinary curriculum. An in-depth study was undertaken at Chattogram Veterinary and Animal Sciences University (CVASU), Bangladesh, where a WBL program has been in place for 20 years. Final-year veterinary students at CVASU were surveyed to ascertain WBL experiences; survey findings were further explored in focus groups with students, recent graduates, faculty, and placement providers. Most agreed that they had sufficient opportunities to observe, assist, and directly handle pet and farm animals with top skills learned, including clinical diagnosis and communication, and recognized the value of learning in professional workplaces. Based on suggested areas of improvement, the following recommendations can be made: carefully selecting placements, adjusting time allocation, improving communication and building strong collaborations with placement providers, allowing students to customize more placements to align with their career preferences, and staffing adequately to arrange placements and manage a WBL program. Overall, results suggest the current WBL arrangements at CVASU are reasonably good, but there are some specific areas for improvement.

Protective effect of Apremilast against LPS-induced acute lung injury via modulation of oxidative stress and inflammation.

Lung injuries are attributed due to exposure to Drugs or chemicals. One of the important challenging situations for the clinicians is to manage treatments of different diseases with acute lung injury (ALI). The objective of this study was to investigate the possible protective mechanisms and action of a novel Phosphodiesterase-4 inhibitor "Apremilast" (AP) in lipopolysaccharide (LPS)-induced lung injury. Blood sample from each animals were collected in a vacuum blood collection tube. The rat lungs were isolated for oxidative stress assessment, western blot analysis and their mRNA expressions using RT-PCR. Exposure of LPS in rats causes significant increase in oxidative stress, activates the pro-inflammatory cytokines release like tissue necrotic factor-alpha (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), modulated gene expression, protein expression and histopathological changes which were reversed by administration of AP. Finding of the research enlighten the protective role of AP against LPS-induced ALI.

The Race to Replace PDE5i: Recent Advances and Interventions to Treat or Manage Erectile Dysfunction: Evidence from Patent Landscape (2016-2021).

For a few decades, globally, erectile dysfunction (ED) has become more prominent even in young adults and represents a mounting health concern causing a significant effect on men's quality of life. There is an expectation that by the end of 2025, the number of ED cases can rise to 322 million. We aimed to comprehensively analyze the scientific output of scholarly articles and studies in the field of ED (2016-2021). Data from scholarly articles were collected using Pubmed, and clinical trials-related information was accessed from the clinical trials website. An extensive patent search was conducted using databases such as USPTO (United States patent and trademark office) and EPO (European patent office), WIPO (World Intellectual Property Organization), etc. Owing to the high market value of ED drugs, considerable interest was attained to grab the opportunities. The race to replace the phosphodiesterase type 5 inhibitor (PDE5 inhibitor-PDE5i) can be identified as evident from the significant number of patents filed and the inventions cleared with clinical trials. Some other intriguing interventions are identified for ED treatment but have yet to gain public acceptance. The current analysis confirms the overall evolution and unexplored corners of research on ED treatment strategies with a current global projection.

Corrigendum to "Protective effect of Apremilast against LPS-induced acute lung injury via modulation of oxidative stress and inflammation" [Saudi J. Biol. Sci. 29(5) (2022) 3414-3424].

[This corrects the article DOI: 10.1016/j.sjbs.2022.02.023.].

Coronavirus disease 2019 and future pandemics: Impacts on livestock health and production and possible mitigation measures.

The World Health Organization declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. COVID-19, the current global health emergency, is wreaking havoc on human health systems and, to a lesser degree, on animals globally. The outbreak has continued since the first report of COVID-19 in China in December 2019, and the second and third waves of the outbreak have already begun in several countries. COVID-19 is expected to have adverse effects on crop production, food security, integrated pest control, tourism, the car industry, and other sectors of the global economy. COVID-19 induces a range of effects in livestock that is reflected economically since human health and livelihood are intertwined with animal health. We summarize the potentially harmful effects of COVID-19 on livestock and possible mitigation steps in response to this global outbreak. Mitigation of the negative effects of COVID-19 and future pandemics on livestock requires the implementation of current guidelines.

Sustainable Antibiotic-Free Broiler Meat Production: Current Trends, Challenges, and Possibilities in a Developing Country Perspective.

Antibiotic-free broiler meat production is becoming increasingly popular worldwide due to consumer perception that it is superior to conventional broiler meat. Globally, broiler farming impacts the income generation of low-income households, helping to alleviate poverty and secure food in the countryside and in semi-municipal societies. For decades, antibiotics have been utilized in the poultry industry to prevent and treat diseases and promote growth. This practice contributes to the development of drug-resistant bacteria in livestock, including poultry, and humans through the food chain, posing a global public health threat. Additionally, consumer demand for antibiotic-free broiler meat is increasing. However, there are many challenges that need to be overcome by adopting suitable strategies to produce antibiotic-free broiler meat with regards to food safety and chicken welfare issues. Herein, we focus on the importance and current scenario of antibiotic use, prospects, and challenges in the production of sustainable antibiotic-free broiler meat, emphasizing broiler farming in the context of Bangladesh. Moreover, we also discuss the need for and challenges of antibiotic alternatives and provide a future outlook for antibiotic-free broiler meat production.

Improvement of DVM Curriculum to Meet OIE Recommendations at Chattogram Veterinary and Animal Sciences University, Bangladesh.

A veterinary education twinning project between Chattogram Veterinary and Animal Sciences University (CVASU) and Tufts Cummings School of Veterinary Medicine (TCSVM) was supported by the World Organisation for Animal Health (OIE) to align CVASU's veterinary curriculum with OIE's recommended Core Curriculum and Day 1 Competencies. The major objectives were curriculum development with improvement to the internship program, introduction of problem-based learning (PBL), and implementation of continuing education (CE). Major activities to achieve these objectives involved several workshops and seminars at CVASU and establishing student exchange and CVASU faculty training programs. Major accomplishments were (a) implementation of a revised Doctor of Veterinary Medicine (DVM) curriculum at CVASU aligned with the OIE-recommended curriculum and Day 1 Competencies; (b) incorporation of PBL into the curriculum and development of 23 PBL cases relevant to Bangladesh-specific diseases; (c) improvement of the internship program by including Day 1 Competencies; (d) development and implementation of 11 structured CE sessions including hands-on training; (e) improvement of curriculum, teaching, and clinical training at CVASU following training of CVASU faculty and students at TCSVM; and (f) three peer-reviewed publications from summer research projects by TCSVM students at CVASU. The twinning project allowed CVASU to improve its DVM curriculum by aligning with OIE's recommended curriculum and Day 1 Competencies. The impact of the project went beyond CVASU as evidenced by other veterinary schools adopting the CVASU curriculum and PBL, veterinary school deans engaged in improving veterinary curriculum and clinical training, and implementation of a national CE program for veterinarians.

Antimicrobial Residues in Chicken and Fish, Chittagong, Bangladesh.

A cross-sectional observation and an intervention study were conducted in Chittagong, Bangladesh in 2015 to assess the status of antimicrobial residues in chicken and fish. The samples were tested for selected antimicrobials (amoxicillin, ciprofloxacin, oxytetracycline and enrofloxacin) using thin-layer chromatography (TLC). The TLC-based overall prevalence of residues was 87.9% in chicken (N = 182) and 56.9% in fish (N = 153). The prevalences in chicken in June (N = 91) and in October (N = 91), respectively, were 91.2% and 83.5% (amoxicillin), 1.1% and 1.1% (enrofloxacin), 1.1% and 0% (ciprofloxacin), and 0% and 6.6% (oxytetracycline). In fish, the prevalence in September (N = 74) and in October (N = 79) was 52.7% and 44.3% (amoxicillin) and 1.4% and 27.8% (oxytetracycline), respectively. The mean concentration of amoxicillin residue was evaluated by ultra-high-performance liquid chromatography to be 508.4 mg/kg (chicken) and 515.4 mg/kg (fish). The random effect model identified market (Chawkbazar vs. Boalkhali: OR 5.7; Steelmill bazar vs. Boalkhali: OR 5.6) as significant factors for amoxicillin residue in chicken. Amoxicillin concentration was significantly reduced in chicken of Kazirhat (ß= - 1.3) and Chawkbazar (ß= - 1.1) and increased in October (ß= 0.77) based on a generalized linear model (GLM). Climbing perch fish had significantly more risk of having amoxicillin residue than that of Bombay duck (OR = 0.05). All samples were treated by washing, boiling and cooking with spices, and then, TLC-based screening of amoxicillin residues was done. A subset of each treated group was evaluated by UHPLC. Treatment reduced amoxicillin residue levels significantly.

Newcastle disease sero and viro-prevalence in rural poultry in Chittagong, Bangladesh.

Bangladesh experiences some of the highest malnutrition rates in the world, and efforts are being made to increase food security and overall health status. One of the largest constrains on increasing food security is endemic diseases among livestock and poultry populations. Newcastle Disease (ND) is one of these viral endemic diseases reducing food security. However, the sero- and viro-prevalence of ND has not been thoroughly studied in rural poultry in Bangladesh. Knowledge of farm management practices and their effect on ND sero and viro-prevalence is needed before interventions can occur, and efforts to improve the endemic state of ND cannot begin without a baseline study. This cross-sectional study randomly sampled 129 rural households with 245 chickens for the sero-prevalence and active infection rate of rural chickens in two selected upazilas (sub-districts) of the Chittagong district. ELISA was used for the detection of sero-prevalence, and cloacal samples were analyzed for ND presence using one-step RT-PCR. The aims of this study were to describe farmer demography, determine the ND sero-prevalence at the household and individual chicken level, estimate the proportionate ND prevalence at the individual chicken level, determine potential risk factors for ND sero-prevalence at the household level, and determine challenges farmers face with household chicken farming. The overall household level ND sero-prevalence based on ELISA was 31.8% (41/129) (95% CI: 23.9-40.6%), whereas the overall bird level ND sero-prevalence based on ELISA was 21.2% (52/245) (95% CI: 16.5-26.8%). ND prevalence based on RT-PCR was 12.5% (4/32) (95% CI: 3.5-29.0%). The odds of ND sero-positivity was significantly higher in farms belonging to Rangunia than in farms belonging to Anowara with an odds ratio (OR) of 7.8 (95% CI: 3.3-18.6%). The odds of ND sero-positivity was significantly lower in poultry house cleaning frequency of once or twice weekly compared with once daily cleaning (OR = 0.3; 95% CI: 0.1-0.8%). High cleaning frequency may produce excessive stress on poultry predisposing them to infection. Poultry rearing is different between Anowara and Rangunia. Anowara (coastal) scavenging areas become restricted because of regular tide flow allowing small fishes and other aquatic animals to be the dominant scavengers in Anowara. The incoming tide also removes viral reservoirs such as feces and dead birds that may otherwise be readily accessed by healthy chickens.

Assessment of hygienic conditions of live bird markets on avian influenza in Chittagong metro, Bangladesh.

Live Bird Markets (LBMs) in Asian countries are considered as hubs for the spread and maintenance of different infectious diseases. In Bangladesh, LBMs are the major source of live and dressed poultry to consumers and until now only a few studies have been conducted targeting infectious agent status such as avian influenza virus (AIV) prevalence of LBMs in Bangladesh. Therefore, a cross sectional study was conducted using all 40 LBMs within the Chittagong Metropolitan Area (CMA) of Bangladesh targeting demographic information and hygienic status of LBMs in concurrence with AIV prevalence and its subtype distribution, as well as the associated risk factors for AIV. Pooled environmental swab samples were collected from 2 to 9 different sites per stall, with epidemiological data being obtained from a total of 290 stalls across 40 LBMs. The samples were evaluated by Real Time Reverse Transcriptase Polymerase Chain Reaction. The prevalence of AIV was 40% (95% CI: 20-60%; N=40) at a LBM level followed by 20.3% (CI: 10-30%, N=290) at a stall level. Specifically, the prevalence of H5, H7 and H9 subtypes at stall level were 2.8% (95% CI: 1-5%), 0% (CI: 0-1.3%) and 3.1% (CI: 1-6%), respectively. Generalized Estimating Equation model identified that the type of species sold (OR=2.5: Chicken and non-duck species versus Duck with other species), bird holding areas (OR=1.9: Cage versus Floor) and Hygienic score (OR=3.1: Score 3 or more versus score less than 3) as potential risk factors for the detection of AIV at stall level. These results suggest that housing chickens and ducks together in the stalls, birds kept on floors, and lack of adequate hygienic measures of the stall were the crucial factors for spreading AIV. This research outcome could be used to develop a proof-based program concerning environmental sanitation along with development of an effective surveillance system to reduce the AIV transmission through LBMs in Bangladesh.

Brace yourself: an unusual case of knee pain, an extradigital glomangioma of the knee.

The differential diagnosis for knee pain is extensive. Glomus tumors comprise approximately 1.6% of soft-tissue tumors in the extremities. Classic subungual tumors occur more frequently in women, whereas ectopic locations are more common in men. Unusual locations include the stomach; lungs; trachea; bones; intestines; fallopian tubes; and intraneural, neuromal, and intravenous locations. We present the case of a 50-year-old man with a 12-year history of enlarging right knee mass found to be a glomangioma. This case report discusses the incidence, presentation, imaging characteristics, histology, and management of glomus tumors of the knee.

p38 MAPK α and ß isoforms differentially regulate plasma membrane localization of MRP2.

In hepatocytes, cAMP both activates p38 mitogen-activated protein kinase (MAPK) and increases the amount of multidrug resistance-associated protein-2 (MRP2) in the plasma membrane (PM-MRP2). Paradoxically, taurolithocholate (TLC) activates p38 MAPK but decreases PM-MRP2 in hepatocytes. These opposing effects of cAMP and TLC could be mediated via different p38 MAPK isoforms (α and ß) that are activated differentially by upstream kinases (MKK3, MKK4, and MKK6). Thus we tested the hypothesis that p38α MAPK and p38ß MAPK mediate increases and decreases in PM-MRP2 by cAMP and TLC, respectively. Studies were conducted in hepatocytes isolated from C57BL/6 wild-type (WT) and MKK3-knockout (MKK3(-/-)) mice and in a hepatoma cell line (HuH7) that overexpresses sodium-taurocholate cotransporting polypeptide (NTCP) (HuH-NTCP). Cyclic AMP activated MKK3, p38 MAPK, and p38α MAPK and increased PM-MRP2 in WT hepatocytes, but failed to activate p38α MAPK or increase PM-MRP2 in MKK3(-/-) hepatocytes. In contrast to cAMP, TLC activated total p38 MAPK but decreased PM-MRP2, and did not activate MKK3 or p38α MAPK in WT hepatocytes. In MKK3(-/-) hepatocytes, TLC still decreased PM-MRP2 and activated p38 MAPK, indicating that these effects are not MKK3-dependent. Additionally, TLC activated MKK6 in MKK3(-/-) hepatocytes, and small interfering RNA knockdown of p38ß MAPK abrogated TLC-mediated decreases in PM-MRP2 in HuH-NTCP cells. Taken together, these results suggest that p38α MAPK facilitates plasma membrane insertion of MRP2 by cAMP, whereas p38ß MAPK mediates retrieval of PM-MRP2 by TLC.

Hydrophobic bile acid apoptosis is regulated by sphingosine-1-phosphate receptor 2 in rat hepatocytes and human hepatocellular carcinoma cells.

The hepatotoxic bile acid glycochenodeoxycholate (GCDC) modulates hepatocyte cell death through activation of JNK, Akt, and Erk. The nonhepatotoxic bile acid taurocholate activates Akt and Erk through the sphingosine-1-phosphate receptor 2 (S1PR2). The role of the S1PR2 in GCDC-mediated apoptosis and kinase activation is unknown. Studies were done in rat hepatocytes, HUH7 cells, and HUH7 cells stably transfected with rat Ntcp (HUH7-Ntcp). Cells were treated with GCDC and apoptosis was monitored morphologically by Hoechst staining and biochemically by immunoblotting for the active cleaved fragment of caspase 3. Kinase activation was determined by immunoblotting with phospho-specific antibodies. JTE-013, an inhibitor of S1PR2, significantly attenuated morphological evidence of GCDC-induced apoptosis and prevented caspase 3 cleavage in rat hepatocytes and HUH7-Ntcp cells. In hepatocytes, JTE-013 mildly suppressed, augmented, and had no effect on GCDC-induced JNK, Akt, and Erk phosphorylation, respectively. Similar results were seen in HUH7-Ntcp cells except for mild suppression of JNK and Erk phosphorylation. Knockdown of S1PR2 in HUH7-Ntcp augmented Akt, inhibited JNK, and had no effect on Erk phosphorylation. GCDC failed to induce apoptosis or kinase activation in HUH7 cells. In conclusion, SIPR2 inhibition attenuates GCDC-induced apoptosis and inhibits and augments GCDC-induced JNK and Akt phosphorylation, respectively. In addition, GCDC must enter hepatocytes to mediate cell death or activate kinases. These results suggest that SIPR2 activation is proapoptotic in GCDC-induced cell death but that this effect is not due to direct ligation of the S1PR2 by the bile acid.

A case of lung volume reduction surgery with decortication for a septic patient in respiratory failure.

INTRODUCTION: Decortication and lung volume reduction surgery are both major operations and each has its independent risk of morbidity and mortality. CASE REPORT: We present the case of a 41 year old gentleman with left sided empyema and giant bullae of the upper lobe with an active air leak that was transferred to our tertiary referral centre for further management. We performed emergency left thoracotomy, decorticated the left lower lobe with extensive lung volume reduction surgery of the upper lobe. Patient's respiratory status significantly improved along with excellent radiological results. CONCLUSION: Our case demonstrates that a combination of complex procedures is feasible with excellent outcomes.

Protein kinase Cδ protects against bile acid apoptosis by suppressing proapoptotic JNK and BIM pathways in human and rat hepatocytes.

Retained bile acids, which are capable of inducing cell death, activate protein kinase Cδ (PKC-δ) in hepatocytes. In nonhepatic cells, both pro- and antiapoptotic effects of PKC-δ are described. The aim of this study was to determine the role of PKC-δ in glycochenodeoxycholate (GCDC)-induced apoptosis in rat hepatocytes and human HUH7-Na-taurocholate-cotransporting polypeptide (Ntcp) cells. Apoptosis was monitored morphologically by Hoechst staining and biochemically by immunoblotting for caspase 3 cleavage. The role of PKC-δ was evaluated with a PKC activator (phorbol myristate acetate, PMA) and PKC inhibitors (chelerythrine, H-7, or calphostin), PKC-δ knockdown, and wild-type (WT) or constitutively active (CA) PKC-δ. PKC-δ activation was monitored by immunoblotting for PKC-δ Thr505 and Tyr311 phosphorylation or by membrane translocation. JNK and Akt phosphorylation and the amount of total bisindolylmaleimide (BIM) were determined by immunoblotting. GCDC induced the translocation of PKC-δ to the mitochondria and/or plasma membrane in rat hepatocytes and HUH7-Ntcp cells and increased PKC-δ phosphorylation on Thr505, but not on Tyr311, in HUH7-Ntcp cells. GCDC-induced apoptosis was attenuated by PMA and augmented by PKC inhibition in rat hepatocytes. In HUH-Ntcp cells, transfection with CA or WT PKC-δ attenuated GCDC-induced apoptosis, whereas knockdown of PKC-δ increased GCDC-induced apoptosis. PKC-δ silencing increased GCDC-induced JNK phosphorylation, decreased GCDC-induced Akt phosphorylation, and increased expression of BIM. GCDC translocated BIM to the mitochondria in rat hepatocytes, and knockdown of BIM in HUH7-Ntcp cells decreased GCDC-induced apoptosis. Collectively, these results suggest that PKC-δ does not mediate GCDC-induced apoptosis in hepatocytes. Instead PKC-δ activation by GCDC stimulates a cytoprotective pathway that involves JNK inhibition, Akt activation, and downregulation of BIM.

A double-blind randomized clinical trial on the efficacy of cortical direct current stimulation for the treatment of Alzheimer's disease.

BACKGROUND: The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation (tDCS) in the neurorehabilitation of Alzheimer's disease (AD). METHODS: Thirty-four AD patients were randomly assigned to three groups: anodal, cathodal, and sham tDCS. Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA, daily for 10 days. Each patient was submitted to the following psychometric assessments: mini-mental state examination (MMSE) and Wechsler adult intelligence scale-third edition at base line, at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions. Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session. RESULTS: Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS. Post hoc comparisons showed that both anodal and cathodal tDCS (ctDCS) improved MMSE in contrast to sham tDCS. Whereas, this was only true for ctDCS in the performance IQ. Remarkably, tDCS also reduced the P300 latency, but had no effect on motor cortex excitability. CONCLUSION: Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency, which is known to be pathologically increased in AD.

Anodal transcranial direct current stimulation over the dorsolateral prefrontal cortex improves anorexia nervosa: A pilot study.

BACKGROUND: Existing treatments for adults with anorexia nervosa (AN) have limited proven efficacy. New treatments that have been suggested involve targeted, brain-directed interventions such as transcranial direct current stimulation (tDCS). We describe findings from seven individuals with treatment-resistant AN who received 10 sessions of anodal tDCS, over the left dorsolateral prefrontal cortex (DLPFC). MATERIAL AND METHOD: In this open-label, single-arm study, seven patients received anodal tDCS (2mA) for 25 minutes over the left dorsolateral prefrontal cortex daily for ten days. Assessments pre-tDCS, post-tDCS and one month later included the Eating Attitude Test (EAT), Eating Disorder Inventory (EDI) and Beck Depression Inventory (BDI). RESULTS: Three patients improved in all three rating scales immediately after the treatment sessions and one month later. Two patients showed improvement at the end of treatment but returned to the baseline after one month. One subject improved only on the BDI scale but not eating scales. The scores in the three rating scales were unaffected by treatment in the remaining patient. There was a significant effect of time (pre, post and 1 month later) on the three rating scores; BDI (P = 0.016), EDI (P = 0.018) and EAT (P = 0.016) and a significant correlation between the percent improvement of BDI and EAT (p = 0.01), and between BDI and EDI (P = 0.006). CONCLUSIONS: These findings suggest that tDCS has potential as an adjuvant treatment for AN and deserves further study.

Rab11, but not Rab4, facilitates cyclic AMP- and tauroursodeoxycholate-induced MRP2 translocation to the plasma membrane.

Rab proteins (Ras homologous for brain) play an important role in vesicle trafficking. Rab4 and Rab11 are involved in vesicular trafficking to the plasma membrane from early endosomes and recycling endosomes, respectively. Tauroursodeoxycholate (TUDC) and cAMP increase bile formation, in part, by increasing plasma membrane localization of multidrug resistance-associated protein 2 (MRP2). The goal of the present study was to determine the role of these Rab proteins in the trafficking of MRP2 by testing the hypothesis that Rab11 and/or Rab4 facilitate cAMP- and TUDC-induced MRP2 translocation to the plasma membrane. Studies were conducted in HuH-NTCP cells (HuH7 cells stably transfected with human NTCP), which constitutively express MRP2. HuH-NTCP cells were transfected with Rab11-WT and GDP-locked dominant inactive Rab11-GDP or with Rab4-GDP to study the role of Rab11 and Rab4. A biotinylation method and a GTP overlay assay were used to determine plasma membrane MRP2 and activation of Rab proteins (Rab11 and Rab4), respectively. Cyclic AMP and TUDC increased plasma membrane MRP2 and stimulated Rab11 activity. Plasma membrane translocation of MRP2 by cAMP and TUDC was increased and inhibited in cells transfected with Rab11-WT and Rab11-GDP, respectively. Cyclic AMP (previous study) and TUDC increased Rab4 activity. However, cAMP- and TUDC-induced increases in MRP2 were not inhibited by Rab4-GDP. Taken together, these results suggest that Rab11 is involved in cAMP- and TUDC-induced MRP2 translocation to the plasma membrane.