Binding of the Magnaporthe oryzae Chitinase MoChia1 by a Rice Tetratricopeptide Repeat Protein Allows Free Chitin to Trigger Immune Responses.

To defend against pathogens, plants have developed complex immune systems, including plasma membrane receptors that recognize pathogen-associated molecular patterns, such as chitin from fungal cell walls, and mount a defense response. Here, we identify a chitinase, MoChia1 (Magnaporthe oryzae chitinase 1), secreted by M. oryzae, a fungal pathogen of rice (Oryza sativa). MoChia1 can trigger plant defense responses, and expression of MoChia1 under an inducible promoter in rice enhances its resistance to M. oryzae MoChia1 is a functional chitinase required for M. oryzae growth and development; knocking out MoChia1 significantly reduced the virulence of the fungus, and we found that MoChia1 binds chitin to suppress the chitin-triggered plant immune response. However, the rice tetratricopeptide repeat protein OsTPR1 interacts with MoChia1 in the rice apoplast. OsTPR1 competitively binds MoChia1, thereby allowing the accumulation of free chitin and re-establishing the immune response. Overexpressing OsTPR1 in rice plants resulted in elevated levels of reactive oxygen species during M. oryzae infection. Our data demonstrate that rice plants not only recognize MoChia1, but also use OsTPR to counteract the function of this fungal chitinase and regain immunity.

Stigma towards mental illness in Asian nations and low-and-middle-income countries, and comparison with high-income countries: A literature review and practice implications.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals' attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

Reduction of Progranulin-Induced Breast Cancer Stem Cell Propagation by Sortilin-Targeting Cyclotriazadisulfonamide (CADA) Compounds.

Cyclotriazadisulfonamide (CADA) compounds selectively down-modulate two human proteins of potential therapeutic interest, cluster of differentiation 4 (CD4) and sortilin. Progranulin is secreted from some breast cancer cells, causing dedifferentiation of receiving cancer cells and cancer stem cell proliferation. Inhibition of progranulin binding to sortilin, its main receptor, can block progranulin-induced metastatic breast cancer using a triple-negative in vivo xenograft model. In the current study, seven CADA compounds (CADA, VGD020, VGD071, TL020, TL023, LAL014, and DJ010) were examined for reduction of cellular sortilin expression and progranulin-induced breast cancer stem cell propagation. In addition, inhibition of progranulin-induced mammosphere formation was examined and found to be most significant for TL020, TL023, VGD071, and LAL014. Full experimental details are given for the synthesis and characterization of the four new compounds (TL020, TL023, VGD071, and DJ010). Comparison of solubilities, potencies, and cytotoxicities identified VGD071 as a promising candidate for future studies using mouse breast cancer models.

Extraordinary Survival Benefits of Severe and Critical Patients with COVID-19 by Immune Modulators: The Outcome of a Clinical Trial in Bangladesh.

BACKGROUND: Coronavirus disease (COVID)-19 has devasted the healthcare delivery system as well as social establishments of almost all countries of the world. However, vaccines for containing new cases of COVID-19 are yet to be realized. Also, presently available antiviral drugs and other standard of care (SOC) management strategies could not satisfactorily control COVID-19-related mortality, which has crossed the one million mark during the last 9 months. These facts present an emergent need for developing new, novel, and evolving therapeutic strategies for the management of COVID-19. AIM AND OBJECTIVE: This cohort study represents a clinical trial in real-life situations in Bangladesh where two immune modulators were applied in patients with severe and critical COVID-19 patients. MATERIALS AND METHODS: A total of 199 confirmed patients of COVID-19 were enrolled in this study. All of them had severe and critical COVID-19 and they were hospitalized at the intensive care unit (ICU) of the Combined Military Hospital (CMH), Dhaka, Bangladesh. All patients were positive for SARS-CoV-2 by polymerase chain reaction (PCR) of the nasal swab and they were endowed with severe pneumonia, multiple organ dysfunctions, and coagulopathy. The median percentage of lung involvement was 65%. The mean oxygen saturation was 83%. The patients received two immune modulators (tocilizumab and bevacizumab) in different combinations to retrieve broader insights about the safety and efficacy of immune modulators in COVID-19 management. RESULTS: Out of the total 199 patients, 122 survived and 77 expired. A single dose of tocilizumab resulted in the survival of 71.5% (73 of 102 COVID-19 patients). On the other hand, a dramatic survival benefit was found in patients receiving bevacizumab (92%). CONCLUSION: The study indicates that active treatment should be started as early as possible for COVID-19 patients as moderate COVID-patients may progress to more severe illnesses with grave consequences. The safety of two immune modulators has been recorded in this cohort of severe and critical COVID-19 patients. In order to have a proper use of these immune modulators, there is a need to accomplish controlled, blinded, and large-scale prospective studies with at least two arms. HOW TO CITE THIS ARTICLE: Islam MA, Mazumder MA, Akhter N, et al. Extraordinary Survival Benefits of Severe and Critical Patients with COVID-19 by Immune Modulators: The Outcome of a Clinical Trial in Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(2):68-75.

Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared as pandemic by World Health Organization (WHO) with increasing morbidity (more than 4.6 million patients) and mortality (300,000 deaths). The world-wide target of management COVID-19 is to reduce complications with available management options; this become highly variable from country to country and even within different regions of the same country. AIM AND OBJECTIVE: This observational prospective study represents a single center study in which all patients in this cohort received almost similar medicines and care. MATERIALS AND METHODS: All patients in this cohort (N: 32) were positive for SARS-CoV-2 by polymerase chain reaction (PCR) with variable presenting symptoms. The management strategy included Standard of Care (SoC) and administration of hydroxychloroquine and doxycycline. Out of 32 patients, 9 patients also received favipiravir. All patients were followed until they were discharged after negativity of SARS-CoV-2 confirmed by PCR on two consecutive occasions taken within 2 days. RESULTS: No death has been recorded in this cohort of 32 patients within the study period. The average hospital staying duration was 13.9 days with a range of 8-21 days. All patients were discharged with improvement of subjective symptoms and SARS-CoV-2 negativity. The vital signs (pulse, blood pressure) as well as and levels of electrolyte and blood counts were within normal and acceptable ranges at the time of discharge. CONCLUSION: The study presented here provide and evidence of a real-life situation of management of limited numbers of COVID-19 patients at a tertiary center of Bangladesh. This study inspires optimism that proper diagnosis, establishment of effective inclusion and exclusion criteria, ensuring application of proper SoC with drugs available in Bangladesh may be a practical option for management of COVID-19 in the country. HOW TO CITE THIS ARTICLE: Huq AKMF, Rahman MF, Islam MA, et al. Real-life Management Strategy of COVID-19 Patients in Bangladesh with No Death: An Observational and Cohort Study. Euroasian J Hepato-Gastroenterol 2020;10(1):31-35.

Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh.

How to cite this article: Al Mahtab M, Huq AKMF, Rahman MF, et al. Therapeutic Endoscopy during COVID-19 Pandemic: An Observational Study from Bangladesh. Euroasian J Hepato-Gastroenterol 2020;10(1): 47-49.