Excessive EP4 Signaling in Smooth Muscle Cells Induces Abdominal Aortic Aneurysm by Amplifying Inflammation.

OBJECTIVE: Excessive prostaglandin E2 production is a hallmark of abdominal aortic aneurysm (AAA). Enhanced expression of prostaglandin E2 receptor EP4 (prostaglandin E receptor 4) in vascular smooth muscle cells (VSMCs) has been demonstrated in human AAAs. Although moderate expression of EP4 contributes to vascular homeostasis, the roles of excessive EP4 in vascular pathology remain uncertain. We aimed to investigate whether EP4 overexpression in VSMCs exacerbates AAAs. Approach and Results: We constructed mice with EP4 overexpressed selectively in VSMCs under an SM22α promoter (EP4-Tg). Most EP4-Tg mice died within 2 weeks of Ang II (angiotensin II) infusion due to AAA, while nontransgenic mice given Ang II displayed no overt phenotype. EP4-Tg developed much larger AAAs than nontransgenic mice after periaortic CaCl2 application. In contrast, EP4fl/+;SM22-Cre;ApoE-/- and EP4fl/+;SM22-Cre mice, which are EP4 heterozygous knockout in VSMCs, rarely exhibited AAA after Ang II or CaCl2 treatment, respectively. In Ang II-infused EP4-Tg aorta, Ly6Chi inflammatory monocyte/macrophage infiltration and MMP-9 (matrix metalloprotease-9) activation were enhanced. An unbiased analysis revealed that EP4 stimulation positively regulated the genes binding cytokine receptors in VSMCs, in which IL (interleukin)-6 was the most strongly upregulated. In VSMCs of EP4-Tg and human AAAs, EP4 stimulation caused marked IL-6 production via TAK1 (transforming growth factor-ß-activated kinase 1), NF-κB (nuclear factor-kappa B), JNK (c-Jun N-terminal kinase), and p38. Inhibition of IL-6 prevented Ang II-induced AAA formation in EP4-Tg. In addition, EP4 stimulation decreased elastin/collagen cross-linking protein LOX (lysyl oxidase) in both human and mouse VSMCs. CONCLUSIONS: Dysregulated EP4 overexpression in VSMCs promotes inflammatory monocyte/macrophage infiltration and attenuates elastin/collagen fiber formation, leading to AAA exacerbation.

Magnetic Carbon Nanofiber Mats for Prospective Single Photon Avalanche Diode (SPAD) Sensing Applications.

Electrospinning enables simple and cost-effective production of magnetic nanofibers by adding nanoparticles to a polymer solution. In order to increase the electrical conductivity of such nanofibers, the carbonization process is crucial. In this study, the chemical and morphological properties of magnetic nanofiber mats prepared from polyacrylonitrile (PAN)/magnetite were investigated. In our previous studies, PAN/magnetite nanofiber mats were carbonized at 500 °C, 600 °C, and 800 °C. Here, PAN/magnetite nanofiber mats were carbonized at 1000 °C. The surface morphology of these PAN/magnetite nanofiber mats is not significantly different from nanofiber mats thermally treated at 800 °C and have remained relatively flexible at 1000 °C, which can be advantageous for various application fields. The addition of nanoparticles increased the average fiber diameter compared to pure PAN nanofiber mats and improved the dimensional stability during thermal processes. The high conductivity, the high magnetization properties, as well as shielding against electromagnetic interference of such carbonized nanofibers can be proposed for use in single photon avalanche diode (SPAD), where these properties are advantageous.

Mass spectrometry-based phospholipid imaging: methods and findings.

Introduction: Imaging is a technique used for direct visualization of the internal structure or distribution of biomolecules of a living system in a two-dimensional or three-dimensional fashion. Phospholipids are important structural components of biological membranes and have been reported to be associated with various human diseases. Therefore, the visualization of phospholipids is crucial to understand the underlying mechanism of cellular and molecular processes in normal and diseased conditions. Areas covered: Mass spectrometry imaging (MSI) has enabled the label-free imaging of individual phospholipids in biological tissues and cells. The commonly used MSI techniques include matrix-assisted laser desorption ionization-MSI (MALDI-MSI), desorption electrospray ionization-MSI (DESI-MSI), and secondary ion mass spectrometry (SIMS) imaging. This special report described those methods, summarized the findings, and discussed the future development for the imaging of phospholipids. Expert opinion: Phospholipids imaging in complex biological samples has been significantly benefited from the development of MSI methods. In MALDI-MSI, novel matrix that produces homogenous crystals exclusively with polar lipids is important for phospholipids imaging with greater efficiency and higher spatial resolution. DESI-MSI has the potential of live imaging of the biological surface while SIMS is expected to image at the subcellular level in the near future.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Nonalcoholic Fatty Liver Disease vs Metabolic-associated Fatty Liver Disease vs Metabolic Dysfunction-associated Steatotic Liver Disease: What's in the Name?

How to cite this article: Singh SP, Sudhamshu KC, Anirvan P, et al. Nonalcoholic Fatty Liver Disease vs Metabolic-associated Fatty Liver Disease vs Metabolic Dysfunction-associated Steatotic Liver Disease: What's in the Name? Euroasian J Hepato-Gastroenterol 2024;14(1):1-4.

Bangladesh records persistently increased number of dengue deaths in recent years: Dissecting the shortcomings and means to resolve.

Objectives: Dengue, a life-threatening disease caused by the mosquito-borne dengue virus, has become a severe problem in recent years in Bangladesh, a South Asian country. In this study, we have critically analyzed the factors contributing to the escalation of the dengue burden in recent years in Bangladesh and discussed the strategies for effective control. Design: This retrospective observational study analyzed the dengue data collected from the five most dengue-affected countries (Bangladesh, Brazil, Mexico, Peru, and the Philippines) from 2019 to 2023. Results: An increased number of dengue-related deaths has been recorded in Bangladesh since 2021. The year 2023 has witnessed a record high dengue-related deaths in Bangladesh, with cumulative deaths for the year surpassing all totals of the previous 23 years (2000-2022: 853 deaths vs 2023: 1705 deaths). Comparing the epidemiologic data of major dengue-endemic countries over the last 5 years, Bangladesh recorded higher dengue fatality rates consecutively for 3 years. Besides the environmental and viral host factors, which are also applicable to many other dengue-endemic countries, there is concern about the failures and mismanagement of authorities to manage dengue patients properly. Conclusion: This study provided evidence that Bangladesh recorded higher dengue fatality rates in recent years. By implementing multi-pronged proactive approaches that can ensure proper prevention programs and appropriate patient management, Bangladesh or similar other countries can significantly reduce the current dengue burden and the associated deaths.

Twenty-five years of Nipah outbreaks in Southeast Asia: A persistent threat to global health.

Objectives: Nipah virus (NiV), a bat-borne zoonotic pathogen, poses persistent threats to global public health due to severe clinical manifestation and high case fatality rate (CFR). A critical examination of NiV outbreaks is essential for refining strategies and mitigating the impact of future infections. In this study, we provide a concise update on global NiV outbreaks that occurred during the past 25 years. Methods: In this geospatial study, we conducted an in-depth examination of the epidemiological characteristics of human NiV cases and deaths from 1998 to 2024 through multiple analyses of public data and official reports. Results: NiV emerged in 1998 in Malaysia during an outbreak among pig farmers. Since then, NiV outbreaks have been documented in five countries of South and Southeast Asia (Bangladesh, India, Malaysia, Philippines, and Singapore). As of May 2024, there have been 754 confirmed human NiV cases with 435 deaths (CFR: 58%) reported in these five countries. Bangladesh records the highest incidence (341 cases and 241 deaths; CFR: 71%) followed by Malaysia (283 cases and 109 deaths; CFR: 39%), India (102 cases and 74 deaths; CFR: 73%), the Philippines (17 cases and nine deaths; CFR: 53%), and Singapore (11 cases and one death; CFR: 9%). Conclusions: The clinical outcomes of NiV have been underscoring constant global public health threats as no effective therapies and vaccines are available. Strong global understandings, with an eye on developing vaccines and therapeutics, are required to minimize clinical outcomes and future threats of NiV.

Electrospun Magnetic Nanofiber Mats for Magnetic Hyperthermia in Cancer Treatment Applications-Technology, Mechanism, and Materials.

The number of cancer patients is rapidly increasing worldwide. Among the leading causes of human death, cancer can be regarded as one of the major threats to humans. Although many new cancer treatment procedures such as chemotherapy, radiotherapy, and surgical methods are nowadays being developed and used for testing purposes, results show limited efficiency and high toxicity, even if they have the potential to damage cancer cells in the process. In contrast, magnetic hyperthermia is a field that originated from the use of magnetic nanomaterials, which, due to their magnetic properties and other characteristics, are used in many clinical trials as one of the solutions for cancer treatment. Magnetic nanomaterials can increase the temperature of nanoparticles located in tumor tissue by applying an alternating magnetic field. A very simple, inexpensive, and environmentally friendly method is the fabrication of various types of functional nanostructures by adding magnetic additives to the spinning solution in the electrospinning process, which can overcome the limitations of this challenging treatment process. Here, we review recently developed electrospun magnetic nanofiber mats and magnetic nanomaterials that support magnetic hyperthermia therapy, targeted drug delivery, diagnostic and therapeutic tools, and techniques for cancer treatment.

A Recent Review of Electrospun Porous Carbon Nanofiber Mats for Energy Storage and Generation Applications.

Electrospun porous carbon nanofiber mats have excellent properties, such as a large surface area, tunable porosity, and excellent electrical conductivity, and have attracted great attention in energy storage and power generation applications. Moreover, due to their exceptional properties, they can be used in dye-sensitized solar cells (DSSCs), membrane electrodes for fuel cells, catalytic applications such as oxygen reduction reactions (ORRs), hydrogen evolution reactions (HERs), and oxygen evolution reactions (OERs), and sensing applications such as biosensors, electrochemical sensors, and chemical sensors, providing a comprehensive insight into energy storage development and applications. This study focuses on the role of electrospun porous carbon nanofiber mats in improving energy storage and generation and contributes to a better understanding of the fabrication process of electrospun porous carbon nanofiber mats. In addition, a comprehensive review of various alternative preparation methods covering a wide range from natural polymers to synthetic carbon-rich materials is provided, along with insights into the current literature.

Journey of Women in Gastroenterology in South Asian Countries: From Training to Leadership.

Women in gastroenterology are underrepresented all over the world and in South Asia, the numbers are even fewer. Women doctors in South Asia have their unique set of problems that they have to deal with. They are trained well and are keen to publish but are not considered good enough. They do not get the same opportunities as their male colleagues. There is more expectation from women doctors to look after their families and children. We can correct this discrepancy by giving more opportunities, arranging flexible training, deserving promotions, leadership roles, equal pay, and research mentors for women doctors in gastroenterology in South Asia, and educating our society to treat women doctors, at par with men. How to cite this article: Kedia D, Kamani L, Begum MR, et al. Journey of Women in Gastroenterology in South Asian Countries: From Training to Leadership. Euroasian J Hepato-Gastroenterol 2023;13(1):41-43.

Electrospinning of Magnetite-Polyacrylonitrile Composites for the Production of Oxygen Reduction Reaction Catalysts.

In this study, electrospun carbon fiber electrodes were prepared by the carbonization of PAN-Fe3O4 electrospun fibers at 800 °C for their use as catalysts in the oxygen reduction reaction in an alkaline electrolyte. Magnetic nanofiber mats were fabricated using a needle-free electrospinning method by incorporating magnetic nanoparticles into a polymer solution. Electrochemical tests revealed that the oxygen reduction reaction (ORR) activity is optimized at an intermediate magnetite loading of 30% wt. These catalysts not only show better performance compared to their counterparts but also achieve high selectivity to water at low potentials. The onset and half-wave potentials of 0.92 and 0.76 V shown by these samples are only slightly behind those of the commercial Pt 20%-carbon black ORR catalyst. The obtained results point out that the electrospinning of PAN-Fe3O4 solutions allows the preparation of advanced N-Fe ORR catalysts in fibrillar morphology.

Endosulfan affects embryonic development synergistically under elevated ambient temperature.

In the present study, we determined the developmental toxicity of endosulfan at an elevated ambient temperature using the zebrafish animal model. Zebrafish embryos of various developmental stages were exposed to endosulfan through E3 medium, raised under two selected temperature conditions (28.5 °C and an elevated temperature of 35 °C), and monitored under the microscope. Zebrafish embryos of very early developmental stages (cellular cleavage stages, such as the 64-cell stage) were highly sensitive to the elevated temperature as 37.5% died and 47.5% developed into amorphous type, while only 15.0% of embryos developed as normal embryos without malformation. Zebrafish embryos that were exposed concurrently to endosulfan and an elevated temperature showed stronger developmental defects (arrested epiboly progress, shortened body length, curved trunk) compared to the embryos exposed to either endosulfan or an elevated temperature. The brain structure of the embryos that concurrently were exposed to the elevated temperature and endosulfan was either incompletely developed or malformed. Furthermore, the stress-implicated genes hsp70, p16, and smp30 regulations were synergistically affected by endosulfan treatment under the elevated thermal condition. Overall, the elevated ambient temperature synergistically enhanced the developmental toxicity of endosulfan in zebrafish embryos.

Role of Biobran (Arabinoxylan Rice Bran) on Patients with Advanced Stage Hepatocellular Carcinoma.

Background and objectives: Carcinoma of liver - renowned, has taken third position in world ranking, comparing to other causes for cancer-related death, however, curative treatment of hepatocellular carcinoma (HCC) is largely absent and even proper management of HCC patients is extremely difficult. The situation becomes more complex when HCC patients are attended by physicians in their terminal state. Arabinoxylan rice bran (biobran) is an inherent product and hemicellulose which is denatured, as well as gained by hemicellulose including a number of hydrolyzing enzymes of carbohydrate from Shiitake mushrooms. It enhances activities of different immune cells and may exert some effects in cancer patients. Materials and methods: In this observation study, the implication of biobran was assessed in a small group of 52 HCC patients. One halves of the patient received biobran and the other halves received best supportive care (BSC). Results: Baseline parameters in two groups were mostly comparable. During observation after 30, 60, and 90 days, a total of six, one, and one patient were alive in biobran group, respectively. The survival of cancer patients of the BSC group was comparable at these time points (6, 1, and 0, respectively) with no statistical significance. After 30 days of treatment, those who were survived in biobran group, the mean CP score was 11.00 ± 1.55 and 10.50 ± 0.84 at pretreatment and posttreatment, respectively, (p = 0.20). Conclusion: Biobran may be of some benefit for terminal HCC, however, more studies are warranted to optimize dose and duration of therapy. How to cite this article: Ashrafujjaman M, Mahtab MA, Noor-E-Alam SM, et al. Role of Biobran (Arabinoxylan Rice Bran) on Patients with Advanced Stage Hepatocellular Carcinoma. Euroasian J Hepato-Gastroenterol 2023;13(2):84-88.

Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.

HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders. How to cite this article: Freyre FM, Aguiar JA, Cinza Z, et al. Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac. Euroasian J Hepato-Gastroenterol 2023;13(2):73-78.

Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern.

Dengue represents one of the most dangerous mosquito-borne viral diseases. Although the disease has been prevalent around the globe over the centuries, recent outbreaks of dengue have devasted the healthcare delivery system of many countries. Being a global infection, dengue virus (DENV) is endemically present mainly in Latin America and Caribbean countries as well as countries in South Asia. The recent outbreak of DENV infection has indicated an exceptional outbreak of DENV in some countries in South Asia. There has been a serious endemic of DENV during 2019. After a heterogeneous pause, another severe outbreak of DENV was reported in some Asian countries in 2023. Among the Asian countries, Bangladesh has reported an acute upsurge of DENV infection in 2023 with record numbers of fatalities. However, this pattern of DENV has not been detected in neighbors of Bangladesh, such as India or other countries in Southeast Asia. This provides an emergent task of dissecting the present DENV infection in Bangladesh from different angles to get insights for future containment of the DENV infection, not only in Bangladesh but also in other DENV endemic areas or DENV-native areas. How to cite this article: Akbar SMF, Khan S, Mahtab M, et al. Recent Dengue Infection in Bangladesh: A Seasonal Endemic Progressing to Year-long Serious Health Concern. Euroasian J Hepato-Gastroenterol 2023;13(2):145-151.

INASL-SAASL Consensus Statements on NAFLD Name Change to MAFLD.

There is an ongoing debate on the change of terminology of non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD). Experts from the Indian National Association for Study of the Liver (INASL) and the South Asian Association for Study of the Liver (SAASL) involved in diagnosing, managing, and preventing NAFLD met in March 2022 to deliberate if the name change from NAFLD to MAFLD is appropriate, as proposed by a group of experts who published a "consensus" statement in 2020. Proponents of name change to MAFLD opined that NAFLD does not reflect current knowledge, and the term MAFLD was suggested as a more appropriate overarching term. However, this "consensus" group which proposed the name change to MAFLD did not represent the views and opinions of gastroenterologists and hepatologists, as well as perceptions of patients across the globe, given the fact that change of nomenclature for any disease entity is bound to have multidimensional impact on all aspects of patient care. This statement is the culmination of the participants' combined efforts who presented recommendations on specific issues concerning the proposed name change. The recommendations were then circulated to all the core group members and updated based on a systematic literature search. Finally, all the members voted on them using the nominal voting technique as per the standard guidelines. The quality of evidence was adapted from the Grades of Recommendation, Assessment, Development and Evaluation system.

Electrospinning Nanofiber Mats with Magnetite Nanoparticles Using Various Needle-Based Techniques.

Electrospinning can be used to produce nanofiber mats containing diverse nanoparticles for various purposes. Magnetic nanoparticles, such as magnetite (Fe3O4), can be introduced to produce magnetic nanofiber mats, e.g., for hyperthermia applications, but also for basic research of diluted magnetic systems. As the number of nanoparticles increases, however, the morphology and the mechanical properties of the nanofiber mats decrease, so that freestanding composite nanofiber mats with a high content of nanoparticles are hard to produce. Here we report on poly (acrylonitrile) (PAN) composite nanofiber mats, electrospun by a needle-based system, containing 50 wt% magnetite nanoparticles overall or in the shell of core-shell fibers, collected on a flat or a rotating collector. While the first nanofiber mats show an irregular morphology, the latter are quite regular and contain straight fibers without many beads or agglomerations. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) reveal agglomerations around the pure composite nanofibers and even, round core-shell fibers, the latter showing slightly increased fiber diameters. Energy dispersive X-ray spectroscopy (EDS) shows a regular distribution of the embedded magnetic nanoparticles. Dynamic mechanical analysis (DMA) reveals that mechanical properties are reduced as compared to nanofiber mats with smaller amounts of magnetic nanoparticles, but mats with 50 wt% magnetite are still freestanding.

Development of Therapeutic Vaccine for Chronic Hepatitis B: Concept, Cellular and Molecular Events, Design, Limitation, and Future Projection.

Four decades have passed since the first usage of the therapeutic vaccine in patients with chronic hepatitis B (CHB). However, there is no approved regimen of vaccine therapy for the treatment of CHB. This is mainly attributable to faulty conception, an improper understanding of the cellular and molecular mechanisms of CHB, and the impaired design of vaccine therapy for CHB. With the advent of new techniques and a better understanding of cellular and molecular mechanisms underlying the genesis of CHB, the limitations and failures of previous regimens of therapeutic vaccines have been primarily understood. Additionally, the importance of immune therapy for treating millions of CHB patients and achieving the target of "Elimination of Hepatitis by 2030" has been focused on in the international arena. This has been amplified by the apparent limitation of commercially available antiviral drugs that are infinite in duration, endowed with safety concerns, and unable to cure liver damage due to their minimal immune modulation capacities. The proposed review article comprehensively discusses each of these points and proposes evidence-based approaches for viable types of vaccine therapy for the treatment of CHB.

A flavone from the ethyl acetate extract of Leea rubra leaves with DNA damage protection and antineoplastic activity.

Among the major constituents of Leea rubra (Family Vitaceae) leaves, phenolic and flavonoind compounds are most important for therapeutic purposes and the plant parts have been used in traditional medicine to treat several diseases for long. Thus, in order to scientifically confirm the traditional uses of the L. rubra leaves, the present study was designed to investigate the efficacy of the isolated flavones against AAPH induced oxidative damage to pUC19 DNA by gel electrophoresis and antineoplastic activity was evaluated on Ehrlich ascites carcinoma (EAC) bearing Swiss albino mice by evaluating percentage inhibition of cell growth, morphological changes of EAC cells and hematological parameters of the mice. The isolation was carried out by column chromatography and structure was revealed by 1H-NMR and 13C NMR. The result shows that, the isolated compound was identified as myricetin 4'-methoxy-3-O-α-l-rhamnopyranoside based on previously reported data. The isolated flavone effectively inhibited AAPH-induced oxidative damage to DNA; because it could inhibit the formation of circular and linear forms of the DNA. In anti-proliferative assay, 76% growth inhibition of EAC cells was observed as compare to the control mice (p<0.05) at a dose 100 mg/kg body weight. Thus the isolated flavone showed great importance as a possible therapeutic agent in preventing oxidative damage to DNA and the chronic diseases caused by such DNA damage, and can also become important in cancer chemotherapy.

Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status.

Nonalcoholic fatty liver disease (NAFLD) is one of the major and prevalent liver diseases from the national and global perspectives. It appears that considerable numbers of the general population have been suffering from NAFLD. When a patient with NAFLD also exhibits inflammation of the liver, the condition is regarded as nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis is a pathological entity that may progress to cirrhosis of the liver (LC) and hepatocellular carcinoma (HCC). It is acceptable by all that the health burden of NAFLD and NASH is tremendous. Due to the increased prevalence of these pathologies, extensive research has been conducted regarding pathogenesis, diagnostic tools, and staging of the diseases. However, adequate and approved pharmacotherapy for these pathologies is lacking. The farnesoid receptor (FXR) is a bile acid-activated receptor. It regulates lipid, glucose, bile acid metabolism. Farnesoid receptor is also endowed with anti-inflammatory and anti-fibrotic properties on the liver. Obeticholic acid (OCA), a potent and selective FXR ligand, may become a promising molecule to combat NASH and advanced fibrosis. The present review briefly discusses the current recommendation of NASH management with available pharmacological treatments. The scope of OCA with a focus on recent data of major randomized controlled trials (RCTs) is discussed. On the basis of current data and recent interim analysis, OCA seems to improve insulin resistance, steatohepatitis, levels of alanine transaminase (ALT) and fibrosis in NASH. Dose-related adverse effects like pruritus and dyslipidemia may limit its usage. Also, its usage may be restricted in patients with NASH cirrhosis. More adequately powered RCTs that would contain NASH patients with different and heterogeneous properties would be required to develop consensus about these issues. The safety profile of different doses of OCA needs to be established in these patients as well as there remain considerable queries about these. How to cite this article: Roy PP, Mahtab MA, Rahim MA, et al. Treatment of Nonalcoholic Steatohepatitis by Obeticholic Acid: Current Status. Euroasian J Hepato-Gastroenterol 2022;12(Suppl 1):S46-S50.