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The middle cerebral artery (MCA) is a major artery supplying blood to the brain and a common site of surgically treatable intracranial aneurysms. The MCA has anatomic variations that may have clinical significance. In order to investigate and document the extent of such variations, the MCA in 100 fresh brain hemispheres from 50 deceased patients, obtained from the Police Surgeon Office, Yangon General Hospital, Myanmar, was dissected and examined. Double MCA was observed in 2% of specimens. The termination patterns were bifurcation (72%), trifurcation (16%), and primary trunk (12%); early bifurcation was also observed (3%). The mean length of the main trunk (MT) was 20.6 ± 6.2 mm. The number of perforators ranged from 4 to 15 (mean = 9); most arose from the MT (96%), and the others originated at the bifurcation point (3%) and in postbifurcation divisions (1%). All of the perforators (100%) had a single branching pattern. The number of cortical branches ranged from 6 to 13 and included the orbitofrontal (98%), prefrontal (99%), precentral (95%), central (98%), temporopolar (87%), anterior temporal (89%), middle temporal (24%), posterior temporal (62%), temporo-occipital (69%), anterior parietal (88%), angular (83%), and posterior parietal (57%) arteries. Early cortical branches emerged from the MT in 52% of specimens. These data can help anatomists, radiologists, and neurosurgeons in preoperative assessment, surgical planning, and selection of surgical approach.

Thin Nyein Nyein Aung,1,2 Ei Thinzar Khin,3 Saiyud Moolphate,4 Chaisiri Angkurawaranon,1,2 Motoyuki Yuasa,5,6 Myo Nyein Aung5– 7 1Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand; 2Global Health and Chronic Conditions Research Group, Chiang Mai University, Chiang Mai, 50200, Thailand; 3Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan; 4Department of Public Health, Faculty of Science and Technology, Chiang Mai Rajabhat University, Chiang Mai, 50300, Thailand; 5Department of Global Health Research, Graduate School of Medicine, Juntendo University, Tokyo, 113-8421, Japan; 6Faculty of International Liberal Arts, Juntendo University, Tokyo, 113-8421, Japan; 7Advanced Research Institute for Health Sciences, Juntendo University, Tokyo, 113-8421, JapanCorrespondence: Myo Nyein Aung, Email myo@juntendo.ac.jpBackground: Non-communicable diseases, including type 2 diabetes (T2DM), are the number one cause of death in Thailand. With its well-known social networking and strong kinship, evidence of social support may be a potential of low-cost approach for T2DM self- management. Social support is quite important for T2DM prevention and control but such evidence in Thai setting is still limited. Therefore, we aimed to study social support and associated determinants for T2DM patients compared to non-diabetes people.Methods: An observational study with a case–control study design was conducted in Chiang Mai, Thailand, in 2019– 2020. Using inclusion and exclusion criteria, a total of 300 participants: 150 cases, 150 controls were recruited. Participants were selected based on outcome status of having “T2DM”. Cases were defined as newly diagnosed (diagnosis of T2DM within 6 months) adult Thai residents and community controls were non-diabetes participants from the same residential area of cases. Data were analyzed by STATA 17. Descriptive analysis compared the characteristics between case and control group. The relation between social support and T2DM was investigated using multivariable Robust regression analysis.Results: About 96.7% of T2DM patients had good social support. T2DM had a significant association with social support in all models defined by potential confounders. Social support was significantly positively associated with having family mealtimes in model 2 and model 3 and increasing age in model 2. BMI and T2DM family history had significant negative association in model 2 and model 3.Conclusion: Social support of Thai T2DM patients is higher than control group. It can either be originated from a newly acquired peer groups network or from the positive social support by family. Future research should focus on behavioral intervention including family and peers to help them understand their role in life-style modification and management of such a prevalent chronic disease.Keywords: diabetes, family, global health, NCDs, social support, Thailand

Background: Postpartum depression (PPD) is non-psychotic depressive illness after childbirth, and PPD affects the health and social status of mothers and their children. This study aims to identify the prevalence of suspected PPD and associated factors among women in Yangon, Myanmar. Methods: This is a cross-sectional study of 552 women at 6–8 weeks postpartum who visited at North Okkalapa General and Teaching Hospital for postnatal care from September to October 2022. Socio-demographic factors, obstetric and infant factors, family support, and medical history were collected using a structured questionnaire. Myanmar version of the Edinburgh Postnatal Depression Scale (EPDS) was used for screening PPD, and all women were divided into suspected PPD (EPDS ≥10) and non-suspected PPD (EPDS

Conclusion: There was no significant association between VEGF +936C/T polymorphism (rs3025039) and preeclampsia among Myanmar pregnant women. However, the findings of this study highlighted that individuals carrying either the CT genotype or the T allele are at a heightened risk of developing preeclampsia. Furthermore, it suggests a potential impact of the gene on the occurrence of preeclampsia, yet the data lacks sufficient evidence to establish statistical significance.

Ishtiaq Ahmad,1 Myo Nyein Aung,2 Satomi Ueno,1 Ei Thinzar Khin,1 Tint Swe Latt,3 Saiyud Moolphate,4 Motoyuki Yuasa1,5 1Department of Public Health, Graduate School of Medicine, Juntendo University, Tokyo, Japan; 2Advanced Research Institute for Health Sciences and Faculty of International Liberal Arts, Juntendo University, Tokyo, Japan; 3Myanmar Diabetes Association (MMDA), Yangon, Myanmar; 4Department of Public Health, Chiang Mai Rajabhat University, Chiang Mai, Thailand; 5Faculty of International Liberal Arts, Juntendo University, Tokyo, JapanCorrespondence: Myo Nyein AungAdvanced Research Institute for Health Sciences and Faculty of International Liberal Arts, Juntendo University, Bunkyo City, Hongo, 2 Chome-1-1, Tokyo, 〒113-8421, JapanTel +813-3813-3111Email myo@juntendo.ac.jpBackground: Despite the evidence that physical activity (PA) can prevent type 2 diabetes mellitus (T2DM), limited research investigated the level of PA among diabetes and non-diabetes in Myanmar, where there is the escalating prevalence of diabetes recently. We investigated PA as modified the risk of diabetes, in a case-control study.Methods: We conducted a case-control study which included 150 cases and 150 controls age 25– 74 years (Mean age 43.3± 14.7 years) among the cases and (55.1± 10.9 years) among the controls, both sex and residence in Yangon. Cases were newly diagnosed with T2DM within six months before data collection, with laboratory-confirmed fasting blood glucose level ≥ 126mg/dl. Controls were community residents, without diabetes, confirmed with a laboratory test. The IPAQ-S was used to assess the PA level. Multiple logistic regression analysis was applied in STATA 15, using the interaction terms for age and PA, adjusting age, sex and BMI.Results: In comparison to controls, cases were older and having less PA knowledge. The levels of vigorous PA were mean 254.9±standard deviations (SD) 845.6 METsmin.wk− 1 among controls, 73.06± 392.1 cases, moderate PA 631.5± 1240.8 METsmin.wk− 1 among controls and 1050.9± 1601.6 cases and walking PA 569.8± 1060 METsmin.wk− 1 among controls and 777.4± 1249 cases, respectively. The multiple logistic regression analysis showed adjusted odds ratios (aOR) 3.84, 95% confidence interval (CI) 1.18– 12.42 (P< 0.05) for those aged 40 and older, with moderate PA and aOR 18.01, Cl 6.45– 50.26 (P< 0.001) for those aged 40 and older, with low PA. Comparing the strength of association, the risk of T2DM among people aged 40 and older with moderate PA is lower than age over 40 with low PA.Conclusion: PA lessened the risk of T2DM, posted by increasing age. The findings highlighted the importance of promoting PA to reduce the T2DM prevalence in the context of Yangon, Myanmar, a low- and middle-income Asian country.Keywords: METs, effect modification, non-communicable disease; risk of diabetes, global health, public health

Epithelioid sarcoma is a soft tissue sarcoma of children and young adults for which the preferred treatment for localised disease is wide surgical resection. Medical management is to a great extent undefined, and therefore for patients with regional and distal metastases, the development of targeted therapies is greatly desired. In this review we will summarize clinically-relevant biomarkers (e.g., SMARCB1, CA125, dysadherin and others) with respect to targeted therapeutic opportunities. We will also examine the role of EGFR, mTOR and polykinase inhibitors (e.g., sunitinib) in the management of local and disseminated disease. Towards building a consortium of pharmaceutical, academic and non-profit collaborators, we will discuss the state of resources for investigating epithelioid sarcoma with respect to cell line resources, tissue banks, and registries so that a roadmap can be developed towards effective biology-driven therapies.

A nine-year-old male with trisomy 21, end-stage renal disease (ESRD) due to reflux nephropathy presented with suspected peritoneal dialysis (PD) catheter-associated peritonitis. One week after receiving an intraperitoneal antibiotic, he presented again with persistent peritonitis symptoms and bloody PD fluid. He underwent exploratory laparotomy, abdominal washout, and PD catheter removal.  Mycobacterium abscessus  ( M. abscessus)  was found in the intraoperative peritoneal fluid culture. After the catheter removal, the child's symptoms significantly improved without antimicrobial medications. He was maintained on hemodialysis three times a week and underwent a successful kidney transplant eight months after this episode. Non-tuberculous mycobacterial peritonitis should be considered in patients with culture-negative peritonitis when there is no intraperitoneal antibiotic response.  M. abscessus  is a rapidly growing atypical Mycobacterium found in the environment and can contaminate medical devices. Our case involved an infection from a contaminated PD catheter since the patient's symptoms improved after PD catheter removal., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khin et al.)

Autosomal recessive polycystic kidney disease (ARPKD) is caused by a mutation in the polycystic kidney and hepatic disease-1 (PKHD1) gene and is an important inherited cause of chronic kidney disease in children. The most typical presentations in neonates are massively enlarged kidneys with variable echogenicity, multiple small cysts, and congenital hepatic fibrosis. Potter sequence with pulmonary hypoplasia can present due to oligohydramnios. Severe pulmonary hypoplasia can lead to respiratory insufficiency and perinatal death. Some affected children can develop end-stage renal disease in early childhood or adolescence. Here, we report the clinical presentations, management, and renal outcomes of three neonatal cases of ARPKD from our center., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Khin et al.)

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro , early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes., Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg- A y /J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined., Results: In vitro , act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM., Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes., Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04424706., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Su, Loo, Gao, Khin, Kong, Dalan, Su, Lee, Ma and Ye.)

Diet-microbiota interactions are emerging as important contributors in the pathogenesis of inflammatory bowel diseases (IBD), characterized by chronic inflammation of the GI tract. The aryl hydrocarbon receptor (AhR) transcription factor regulates xenobiotic metabolism and is activated by exogenous ligands, including indole-3-carbinole (I3C), which is found in cruciferous vegetables. However, studies investigating the impact of dietary I3C and AhR in preclinical models resembling human IBD are lacking. Mice (WT or AhR KO in IECs, 6-8 weeks) or SAMP/YitFC and AKR/J control (4 weeks, m/f) were fed an AhR ligand-depleted or I3C (200 ppm)-supplemented diet. There were increased levels of LPS and exacerbated inflammation, resulting in increased mortality in AhR ΔIEC mice fed the AhR ligand-depleted diet in response to chronic DSS. The mechanisms underlying the protective effects of I3C supplementation during colonic colitis involved amelioration of intestinal inflammation and restoration of the altered gut microbiota, particularly the families of clostridicae and lachnospriaceae. Furthermore, the AhR-depleted diet led to the emergence of pathobiont Parvibacter caecicola in WT mice. SAMP/YitFc mice with spontaneous ileitis showed significant recovery in epithelial abnormalities when fed dietary I3C. These data demonstrate the critical role of AhR and the mechanisms of dietary I3C in maintaining epithelial homeostasis and ameliorating inflammation.

Background: IgA vasculitis (IgAV) is the most common type of vasculitis in children. There is a lack of consensus for management of significant IgAV nephritis (IgAVN). This study was designed to identify the most used treatment options and describe their efficacy., Methods: This is a multicenter retrospective study of children age 1-21 years with IgAVN who were managed for at least 6 months by a nephrologist. Subjects with at least microscopic hematuria and proteinuria and/or decreased kidney function were enrolled. Kidney outcome was assessed by eGFR and urine protein/creatinine (UPC) ratios at 2-4 weeks, 3, 6, and 12 months post-diagnosis., Results: A total of 128 subjects with median age of 7 years (range 2-18) were included. Of these, 69 subjects had kidney biopsy with crescents detected in 53%. AKI (P = 0.039), nephrosis (P = 0.038), and crescents on biopsy (P = 0.013) were more likely in older patients. Patients with UPC > 1 mg/mg were more likely to get a kidney biopsy (P < 0.001) and to be treated with steroids ± immunosuppressive (IS) agents (P = 0.001). Sixty-six percent of patients were treated with steroids and/or IS agents for variable durations. Anti-metabolite agents were the most common IS agents used with variability in dosing and duration. At 12 months, most subjects had a normal eGFR (79%) (median 123, range 68-207 mL/min/1.73 m 2 ) and no proteinuria (median UPC 0.15, range 0.01-4.02 mg/mg)., Conclusions: IS agents are frequently used in managing IgAVN associated with heavy proteinuria, nephrosis, and/or AKI. Prospective studies are needed to determine indications and needed duration of IS therapy. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Competing Interests: All authors have nothing to disclose.

The middle cerebral artery (MCA) is a major artery supplying blood to the brain and a common site of surgically treatable intracranial aneurysms. The MCA has anatomic variations that may have clinical significance. In order to investigate and document the extent of such variations, the MCA in 100 fresh brain hemispheres from 50 deceased patients, obtained from the Police Surgeon Office, Yangon General Hospital, Myanmar, was dissected and examined. Double MCA was observed in 2% of specimens. The termination patterns were bifurcation (72%), trifurcation (16%), and primary trunk (12%); early bifurcation was also observed (3%). The mean length of the main trunk (MT) was 20.6 ± 6.2 mm. The number of perforators ranged from 4 to 15 (mean = 9); most arose from the MT (96%), and the others originated at the bifurcation point (3%) and in postbifurcation divisions (1%). All of the perforators (100%) had a single branching pattern. The number of cortical branches ranged from 6 to 13 and included the orbitofrontal (98%), prefrontal (99%), precentral (95%), central (98%), temporopolar (87%), anterior temporal (89%), middle temporal (24%), posterior temporal (62%), temporo-occipital (69%), anterior parietal (88%), angular (83%), and posterior parietal (57%) arteries. Early cortical branches emerged from the MT in 52% of specimens. These data can help anatomists, radiologists, and neurosurgeons in preoperative assessment, surgical planning, and selection of surgical approach., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2021 Eve M. Oo et al.)

Titin-truncating variants (TTNtv) are the most common genetic cause of dilated cardiomyopathy. TTNtv occur in ~1% of the general population and causes subclinical cardiac remodeling in asymptomatic carriers. In rat models with either proximal or distal TTNtv, we previously showed altered cardiac metabolism at baseline and impaired cardiac function in response to stress. However, the molecular mechanism(s) underlying these effects remains unknown. In the current study, we used rat models of TTNtv to investigate the effect of TTNtv on autophagy and mitochondrial function, which are essential for maintaining cellular metabolic homeostasis and cardiac function. In both the proximal and distal TTNtv rat models, we found increased levels of LC3B-II and p62 proteins, indicative of diminished autophagic degradation. The accumulation of autophagosomes and p62 protein in cardiomyocytes was also demonstrated by electron microscopy and immunochemistry, respectively. Impaired autophagy in the TTNtv heart was associated with increased phosphorylation of mTOR and decreased protein levels of the lysosomal protease, cathepsin B. In addition, TTNtv hearts showed mitochondrial dysfunction, as evidenced by decreased oxygen consumption rate in cardiomyocytes, increased levels of reactive oxygen species and mitochondrial protein ubiquitination. We also observed increased acetylation of mitochondrial proteins associated with decreased NAD+/NADH ratio in the TTNtv hearts. mTORC1 inhibitor, rapamycin, was able to rescue the impaired autophagy in TTNtv hearts. In summary, TTNtv leads to impaired autophagy and mitochondrial function in the heart. These changes not only provide molecular mechanisms that underlie TTNtv-associated ventricular remodeling but also offer potential targets for its intervention., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The role of nonfictional and fictional media in suicide contagion has been well established, ostensibly beginning with the publication of Goethe's The Sorrows of Young Werther in 1774. In recent decades, the emergence of several new forms of media (e.g. websites, social media, blogs, smartphone applications) has revolutionized the communication and social interaction paradigms. This article reviews "the Werther effect" (or suicide contagion related to media), special populations who are more influential or susceptible, current media reporting guidelines and their effectiveness, and the latest research on new media and its effect on suicide and suicide contagion. The aim is to update recommendations on how to mitigate the potential negative effects of both traditional and new media on suicidal behavior and suicide contagion., (Copyright © 2018 John Wiley & Sons, Ltd.)

Fibrosis is a common pathology in cardiovascular disease. In the heart, fibrosis causes mechanical and electrical dysfunction and in the kidney, it predicts the onset of renal failure. Transforming growth factor β1 (TGFβ1) is the principal pro-fibrotic factor, but its inhibition is associated with side effects due to its pleiotropic roles. We hypothesized that downstream effectors of TGFβ1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicity. Here we show, using integrated imaging-genomics analyses of primary human fibroblasts, that upregulation of interleukin-11 (IL-11) is the dominant transcriptional response to TGFβ1 exposure and required for its pro-fibrotic effect. IL-11 and its receptor (IL11RA) are expressed specifically in fibroblasts, in which they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il-11 injection causes heart and kidney fibrosis and organ failure, whereas genetic deletion of Il11ra1 protects against disease. Therefore, inhibition of IL-11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These results reveal a central role of IL-11 in fibrosis and we propose that inhibition of IL-11 is a potential therapeutic strategy to treat fibrotic diseases.

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ∼1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease., Competing Interests: S.A.C. consults for Illumina.

Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases.

The cognitive and behavioral changes that can be observed in the neurodegenerative terminal disease amyotrophic lateral sclerosis (ALS), once characterized as purely a motor neuron disease, have become increasingly recognized over the past century. Detecting cognitive deficits earlier and identifying continued changes at regular intervals can lead to improved care, proactive treatments, and earlier discussions about end-of-life wishes. Although medical decisional capacity is required for every treatment decision made, its importance becomes paramount when making decisions on complex medical treatments that will invariably and significantly affect quality of life or life itself. In this review, we conducted a critical analysis of the evidence-based literature on the cognitive and behavioral impairments in ALS that can compromise medical decisional capacity. We review specific ALS-related clinical scenarios in which decisional capacity is of utmost importance and discuss a practical framework for cognitive and behavioral assessment that can be routinely and efficiently used, while being mindful of the confounding factors associated with ALS. Finally, we review models for preserving patient choices that can be used in patients with ALS to help safeguard autonomy and retain dignity toward the end of life., (© 2015 American Academy of Psychiatry and the Law.)

The transgender inmate population presents unique challenges and opportunities in medical, psychiatric, and correctional systems of care worldwide. We present a review of both case law and efforts within the medical and psychiatric communities to address transgender needs more consistently over the past few decades. In addition, we discuss the standardized implementation of core principles within the correctional system that should provide comprehensive care to transgender inmates.

Cadherin-17 (CDH17) is an oncofetal molecule associated with poor prognostic outcomes of hepatocellular carcinoma (HCC), for which the treatment options are very limited. The present study investigates the therapeutic potential of a monoclonal antibody (Lic5) that targets the CDH17 antigen in HCC. In vitro experiments showed Lic5 could markedly reduce CDH17 expression in a dose-dependent manner, suppress β-catenin signaling, and induce cleavages of apoptotic enzymes caspase-8 and -9 in HCC cells. Treatment of animals in subcutaneous HCC xenograft model similarly demonstrated significant tumor growth inhibition (TGI) using Lic5 antibody alone (5 mg/kg, i.p., t.i.w.; ca.60-65% TGI vs. vehicle at day 28), or in combination with conventional chemotherapy regimen (cisplatin 1 mg/kg; ca. 85-90% TGI). Strikingly, lung metastasis was markedly suppressed by Lic5 treatments. Immunohistochemical and western blot analyses of xenograft explants revealed inactivation of the Wnt pathway and suppression of Wnt signaling components in HCC tissues. Collectively, anti-CDH17 antibody promises as an effective biologic agent for treating malignant HCC.

Cumulative evidences(s) have established that the constitutive activation of STAT3 plays a pivotal role in the proliferation, survival, metastasis, and angiogenesis and thus can contribute directly to the pathogenesis of hepatocellular carcinoma (HCC). Thus, novel agents that can inhibit STAT3 activation have potential for both prevention and treatment of HCCs. The effect of celastrol on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was investigated. The in vivo effect of celastrol on the growth of human HCC xenograft tumors in athymic nu/nu mice was also examined. We observed that celastrol inhibited both constitutive and inducible STAT3 activation, and the suppression was mediated through the inhibition of activation of upstream kinases c-Src, as well as Janus-activated kinase-1 and -2. Vanadate treatment reversed the celastrol-induced modulation of STAT3, suggesting the involvement of a tyrosine phosphatase. The inhibition of STAT3 activation by celastrol led to the suppression of various gene products involved in proliferation, survival, and angiogenesis. Celastrol also inhibited the proliferation and induced apoptosis in HCC cells. Finally, when administered intraperitoneally, celastrol inhibited STAT3 activation in tumor tissues and the growth of human HCC xenograft tumors in athymic nu/nu mice without any side effects. Overall, our results suggest for the first time that celastrol exerts its antiproliferative and proapoptotic effects through suppression of STAT3 signaling in HCC both in vitro and in vivo., (2012 AACR)

Dipeptidyl peptidase IV (DPPIV/CD26) is a multifunctional cell surface aminopeptidase that is widely expressed in different cell types. Our previous study demonstrated a possible link between DPPIV expression and decreased i.p. dissemination and loss of invasive potential of ovarian carcinoma. In this report, we examined the mechanisms of the anti-invasive ability of DPPIV in greater detail. Expression of E-cadherin and beta-catenin was positively correlated with DPPIV expression among five independent ovarian carcinoma cell lines. The introduction of DPPIV cDNA into an ovarian carcinoma cell line (SKOV3) with low DPPIV expression enhanced the expression of E-cadherin and beta-catenin, with a cellular morphological change from a fibroblastic and motile phenotype to an epithelial phenotype. In addition, matrix metalloproteinase 2 and membrane type 1 matrix metalloproteinase, important markers associated with invasive and metastatic potential, were remarkably reduced. In contrast, tissue inhibitors of matrix metalloproteinases were up-regulated by DPPIV transfection. Furthermore, suppression of the phosphorylation levels of mitogen-activated protein kinase isoform, extracellular signal-regulated kinase, was observed in DPPIV-overexpressing cells. To our knowledge, this is the first evidence that increasing DPPIV expression may contribute to prolonged survival by up-regulation of E-cadherin and tissue inhibitors of matrix metalloproteinases.

This prospective cohort study was carried out in the neonatal unit of the Yangon Children Hospital, Myanmar, to gather more information on the types of feedings and hand-washing practices of mothers as the determinant of severe dehydration in infants with acute diarrhoea due to Escherichia coli. The study subjects included 100 infants with diarrhoea, aged less than 4 months, admitted to the hospital from June 1997 to May 1998. Data on isolation of E. coli from rectal swab samples, types of feedings, hand-washing practices, and dehydration status were collected. Of the 100 cases, E. coli was isolated from rectal swab samples of 48 infants. Of these 48 cases, 28 had some dehydration and 20 had severe dehydration. Exclusive breast-feeding was observed only in the age group < 1 and > 1-2 month(s). The association of the severity of dehydration with other types of feedings compared to exclusive breast-feeding was not statistically significant. In this study, most mothers washed their hands with water only after cleansing their children's defaecation, and before and after feeding their children. The severity of dehydration was statistically significant in hand-washing practices when compared to washing with water only and washing with soap and water. This study has shown the association between types of feedings and hand-washing practices with dehydration in infants with acute diarrhoea due to E. coli. The results of the study suggest that there is a need for appropriate intervention programmes to promote exclusive breast-feeding and hand-washing practices with soap and water after cleansing children's defaecation, and before and after feeding children.