Four New Cytotoxic Arborinane-Type Triterpenes from the Endolichenic Fungus Myrothecium inundatum.

Two new arborinane-type triterpenes, myrotheols A (1: ) and B (2: ), two new arborinane-type glycosides, myrothesides C (3: ) and D (4: ), together with four known diterpenes (5:  - 8: ) were isolated from the ethyl acetate extract of the endolichenic fungus Myrothecium inundatum. The structures of new compounds 1:  - 4: were elucidated by NMR and MS analyses. The absolute configuration of 1: was assigned by a single-crystal X-ray diffraction experiment. Compounds 3: and 4: represent the first two natural 4-O-methyl-α-D-mannosides. Compounds 1:  - 8: exhibited cytotoxicity against K562 and RKO human cancer cell lines.

Cytotoxic Secondary Metabolites from the Endolichenic Fungus Hypoxylon fuscum.

As part of our search for new cytotoxic and antimicrobial natural products from endolichenic fungi, 19 compounds including 1 new 10-member lactone (2: ), 1 new polyacetylene glycoside (3: ), 1 new brasilane-type sesquiterpenoid glycoside (4: ), and 2 isobenzofuran-1(3H)-one derivatives (5: and 6: ) were isolated from the solid culture of the endolichenic fungus Hypoxylon fuscum. Their structures were unambiguously elucidated by NMR spectroscopic data, MS, ECD (electronic circular dichroism) calculation, and chemical methods. The cytotoxic effects on K562, SW480, and HEPG2 cell lines and the antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were assessed. Compounds 1, 2: , and 5: exhibited moderate cytotoxicity against K562, SW480, and HEPG2 cell lines while compounds 1, 9: , and 11: displayed weak antibacterial activity against S. aureus.

A systematic review on ethnomedicines of anti-cancer plants.

Cancer is a serious health problem and the second leading cause of death around the globe. Present review is an attempt to provide utmost information based on ethno-pharmacological and toxicological aspects of anti-cancer plants of the world. A total of 276 articles published in English journals and containing maximum ethnomedicinal information were reviewed using several data sources such as; Google scholar, Web of Science, Scopus, PubMed and floras of different countries. A total of 199 anti-cancer plants were recorded in present review and results indicated that traditional medicines are mostly being use in developing countries for cancer treatment. Traditionally and scientifically skin and breast cancer types gained more focus. Seventy plants were reportedly analyzed for in-vitro activities while 32 plants were having in-vivo reports. Twenty nine pure compounds (mostly phenolic) were reportedly isolated from anti-cancer plants and tested against different cancer cell lines. Inspite having better efficiency of ethnomedicines as compared to synthetic drugs, several plants have also shown toxic effects on living system. Therefore, we invite researchers attention to carry out detailed ethno-pharmacological and toxicological studies on un-explored anti-cancer plants in order to provide reliable knowledge to the patients and develop novel anti-cancer drugs. Copyright © 2017 John Wiley & Sons, Ltd.

Overview on Thioredoxin-Interacting Protein (TXNIP): A Potential Target for Diabetes Intervention.

BACKGROUND: Diabetes mellitus (DM) is a common metabolic disorder characterized by a persistent increment of blood glucose. Type 2 DM is characterized by insulin resistance and ß-cell dysfunction. Thioredoxin-interacting protein (TXNIP) is among the factors that control the production and loss of pancreatic ß-cells. OBJECTIVE: Recent studies have shown that high glucose can significantly up-regulate the expression of the TXNIP. Overexpression of TXNIP in ß-cells not only induced apoptosis but also decreased the production of insulin. At the same time, TXNIP deficiency protected the apoptosis of ß-cells, leading to increased insulin production. Therefore, finding small molecules that can modulate TXNIP expression and downstream signalling pathways is essential. Thus, the inhibition of TXNIP has beneficial effects on the cardiovascular system and other tissues such as the heart and the kidney in DM. Therefore, DM treatment must target small TXNIP activity, inhibit expression, and promote endogenous cell mass and insulin production. CONCLUSION: This review briefly describes the effect mechanism, regulatory mechanism, and crystal structure of TXNIP. In addition, we highlight how TXNIP signalling networks contribute to diabetes and interact with drugs that inhibit the development often and its complexes. Finally, the current status and prospects of TXNIP targeted therapy are also discussed.

Knowledge, practice and psychological symptoms among medical laboratory staff during COVID-19 pandemic in Nepal: An online based survey.

INTRODUCTION: Despite several attempts to control COVID-19, there was a continuous rise in the number of cases, and this has left questions unanswered on the availability of health resources in Nepal. Here, we tried to assess the level of knowledge, practice and psychological symptoms among medical laboratory staff. METHODS: An online survey was conducted in February 2021. A total of 301 completely filled responses were used to assess knowledge, practice and psychological distress. R-language software was used for data analysis and p-value less than 0.05 was considered statistically significant. RESULTS: Of the total 301 respondents, 180 (59.8%) were male and 121 (40.2%) were female. The average score of knowledge obtained in this study was 32.4 ± 5.7 on a 56-point scale. Knowledge level was significantly different among age-groups (p-value - 0.034). The average practice score obtained was 2.25 ± 0.91 on a 4-point scale. More than one psychological distress symptom was observed in nearly half (41.5%) of the participants. CONCLUSION: We conclude that medical laboratory staff in Nepal has satisfactory levels of knowledge and practice and, larger number of them has psychological distress. The study recommends further improvement in an effective information flow system, regular training, social security and psychological support.

A non-traditional dietary pattern increases risk of coronary artery disease in the Nepalese population.

OBJECTIVES: Several dietary patterns are associated with cardiovascular diseases. Traditional, Western, Mediterranean, and vegetarian are common dietary patterns, derived from principal component analysis (PCA) of dietary food intakes associated with cardiovascular diseases; however, these patterns were derived mostly from the diet habits of people in Western and European countries. Therefore, the present study aimed to determine dietary patterns linked with coronary artery disease (CAD) in the Nepalese population. METHODS: Food frequency questionnaires were used to estimate dietary intakes in 306 people with CAD and 306 people in a control group matched for age and sex. PCA was performed to deduce the dietary patterns, and conditional logistic regression was executed to determine the association of the dietary patterns with CAD. RESULTS: The component of PCA with higher loadings of refined grain, sugar, and meat and lower loadings of milk, whole grain, and fruit was named the non-traditional dietary pattern in the present study. We found a 34% increased risk of CAD (odds ratio, 1.34; 95% confidence interval, 1.14-1.58; P < 0.001) associated with this dietary pattern after adjusting for smoking, physical activity, and cardiometabolic risk factors. Dietary-pattern scores were further categorized into tertiles, and the third tertile was observed with significanly higher odds of CAD than the first tertile (odds ratio, 2.32; 95% confidence interval, 1.3-4.14; P for trend = 0.004). CONCLUSIONS: PCA-derived non-traditional dietary patterns can be a risk for developing CAD in Nepalese people. However, further cohort studies or randomized community trials are suggested to confirm our findings.

Medical laboratory staff satisfaction and their perspective on the role of health institutions to combat COVID-19 pandemic.

OBJECTIVE: To assess the facilities and challenges encountered in the clinical laboratories, satisfaction of the medical laboratory staff (MLS) toward their profession and their views on the role of related health institutions during the first wave of the Coronavirus Disease 2019 (COVID-19) pandemic in Nepal. METHODS: A web-based cross-sectional study was conducted among registered MLS in Nepal. Data were collected using a structured self-reported questionnaire on the Google Docs platform. RESULTS: A total of 301 respondents were enrolled in the study; of which 180 were male and 121 were female. Of the 301 respondents, a lack of infrastructure was reported by 241 (80.1%), a lack of skill development training by 204 (67.8%), limited availability of diagnostics kits by 151 (50.2%), overburdened by the workload by 142 (47.2%) and difficulty in sample management by 129 (42.9%). A total of 244 of 301 respondents (81.1%) believed that stakeholder institutions should collaborate with the government during the pandemic. The level of satisfaction during the pandemic (130 of 301; 43.19%) was found to have decreased compared with before the pandemic (203 of 301; 67.4%). CONCLUSION: MLS were not fully satisfied with the available resources during the pandemic.

Prospects for controlling future pandemics of SARS in highlights of SARS-CoV-2.

Throughout human history infectious diseases have emerged to become global threats once in a while. Sometimes the previously established infections surfaced due to geographical extension or by increasing their transmissibility or pathogenicity while in other instances new infections have periodically emerged by transmitting from animals to humans. A proper strengthening of the existing health care system, disease surveillance, advancement in medical technology and healthy lifestyle is a must for controlling the future re-emergence of pandemics. Similarly, a deeper understanding of (1) key medical and social elements; (2) treatment and prevention options; (3) epidemic preparedness of the health care system; and (4) investing in ethno medicine research is necessary to prevent the future devastating pandemic emergencies.

Awareness of aerosol-related transmission of COVID-19 among the dentists of Nepal.

OBJECTIVE: To access the awareness of dental practitioners of Nepal towards COVID-19 transmission through aerosols. MATERIALS AND METHODS: The study involved 384 dentists from all over Nepal and was conducted for a period of 3 months. A self-reported online questionnaire was developed using Google forms and the link was shared. It emphasized the awareness related to the aerosol and ventilation system in their daily practices was prepared. The data were analyzed in Statistical Package for Social Sciences version 20.0 software. RESULTS: The majority of participants were female 52.9% (n = 203) and within the age groups of <30 years 57% (n = 219). Participants from Bagmati Province were 60.4% (n = 232), with least from Sudurpaschim Province 0.5% (n = 2). 60% of participants provided only emergency services during the COVID-19 pandemic and few (7%) provided consultations via telephone. The current ventilation system used was a well-ventilated room with open windows 65.4% (n = 251). However, 52.8% (n = 203) preferred specialized operatory incorporating high-efficiency particulate air (HEPA) filters and ultraviolet (UV) light. More than 60% of respondents were unaware of the particle size of the aerosol. CONCLUSIONS: The obtained results signify the need for the proper ventilation system with appropriate air filtration systems in dental clinical setups.

Optimization of Growth Conditions and Biological Activities of Nepalese Ganoderma lucidum Strain Philippine.

Ganoderma lucidum has been extensively studied for its valuable medicinal importance. In this study, the artificial cultivation of G. lucidum strain Philippine in different culture media, including sawdust substrate, was performed and optimized on the Potato Dextrose Agar (PDA) media. Phytochemical, antibacterial, and antioxidant analyses were performed and compared between the ethanol extracts prepared from two different cultures (fruit from synthetic log culture and mycelia from PDA media culture). Both the 200 mg/mL and 100 mg/mL concentrations of extracts inhibited all the tested bacteria, and the results were promising than the corresponding control using antibiotics. The fruit extract showed higher antioxidant potential (150.6 ± 56.92 mg ascorbic acid equivalent/g extract) than mycelial extract (144.28 ± 81.72 mg ascorbic acid equivalent/g extract). The results indicate that fruiting bodies of G. lucidum cultivated in a complex dust medium possess higher antioxidant properties than mycelia culture, which can be further explored for therapeutic applications.

In vitro Antimicrobial Synergy Testing of Extensively Drug-Resistant Clinical Isolates at an Organ Transplant Center in Nepal.

PURPOSE: Inappropriate use of broad-spectrum antibiotics contributes to the emergence of multidrug-resistant (MDR) bacteria. Finding novel antimicrobial agents and strategies based on synergistic combinations are essential to combat MDR infections. This study was designed to determine in vitro synergy of different antimicrobials against extensively drug-resistant (XDR) Gram-negative clinical isolates. METHODS: A descriptive, cross-sectional study was conducted at Human Organ Transplant Center, Nepal, for five months. Clinical isolates were checked for their drug-resistance properties including extended-spectrum beta-lactamase- (ESBL-) and metallo-beta-lactamase- (MBL-) production. The XDR isolates were further tested for antimicrobial synergy, and the results were interpreted as synergistic, additive, indifferent or antagonistic determining fractional inhibitory concentration of the antibiotics. RESULTS: Out of total 1155 clinical samples, 308 showed significant growth. Escherichia coli was the most common isolate (n=142) followed by Klebsiella pneumoniae, Acinetobacter calcoaceticus baumannii (Acb) complex, Pseudomonas aeruginosa and miscellaneous bacteria. Out of the culture positive isolates, 21.4% were MDR and 10.06% were XDR. The XDR population comprised K. pneumoniae (18.42%), E. coli (9.86%), Acb complex (7.41%) and P. aeruginosa (4.17%). Among the culture positive isolates, 4.5% and 5.8% were ESBL- and MBL-producers, respectively. Colistin, polymyxin B, and tigecycline were the antibiotics effective in majority of MDR isolates as compared to carbapenems. The combination of antibiotics - meropenem and colistin showed the highest proportion of "synergy" among all XDR E. coli whereas the combination of amikacin and colistin showed synergistic effect in XDR K. pneumoniae. CONCLUSION: A significant proportion of isolates were MDR among which a large fraction was XDR. The combination of meropenem, amikacin and colistin with one another in pair showed beneficial activity in vitro. Such combinations can be utilized as effective therapy for XDR infections. Further studies are required to confirm these findings, and accordingly treatment protocols should be developed in the management of such infections.

Combating the COVID-19 Pandemic: Experiences of the First Wave From Nepal.

Unprecedented and unforeseen highly infectious Coronavirus Disease 2019 (COVID-19) has become a significant public health concern for most of the countries worldwide, including Nepal, and it is spreading rapidly. Undoubtedly, every nation has taken maximum initiative measures to break the transmission chain of the virus. This review presents a retrospective analysis of the COVID-19 pandemic in Nepal, analyzing the actions taken by the Government of Nepal (GoN) to inform future decisions. Data used in this article were extracted from relevant reports and websites of the Ministry of Health and Population (MoHP) of Nepal and the WHO. As of January 22, 2021, the highest numbers of cases were reported in the megacity of the hilly region, Kathmandu district (population = 1,744,240), and Bagmati province. The cured and death rates of the disease among the tested population are ~98.00 and ~0.74%, respectively. Higher numbers of infected cases were observed in the age group 21-30, with an overall male to female death ratio of 2.33. With suggestions and recommendations from high-level coordination committees and experts, GoN has enacted several measures: promoting universal personal protection, physical distancing, localized lockdowns, travel restrictions, isolation, and selective quarantine. In addition, GoN formulated and distributed several guidelines/protocols for managing COVID-19 patients and vaccination programs. Despite robust preventive efforts by GoN, pandemic scenario in Nepal is, yet, to be controlled completely. This review could be helpful for the current and future effective outbreak preparedness, responses, and management of the pandemic situations and prepare necessary strategies, especially in countries with similar socio-cultural and economic status.

Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: Potential Targets for Gout Intervention.

BACKGROUND: Gout, inflammatory arthritis caused by the deposition of monosodium urate crystals into affected joints and other tissues, has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. OBJECTIVE: In recent years, the development of targeted drugs in gout has made significant achievements. The global impact of gout continues to increase, and as a result, the focus of disease-modifying therapies remains elusive. In addition, the characterization of available instrumental compounds is urgently needed to explore the use of novel selective and key protein-ligand interactions for the effective treatment of gout. Xanthine oxidase (XO) is a key target in gout to consider the use of XO inhibitors in patients with mild to moderate condition, however, the costs are high, and no other direct progress has been made. Despite many XO inhibitors, a selective potent inhibitor for XO is limited. Likewise, in recent years, attention has been focused on different strategies for the discovery and development of new selectivity ligands against transforming growth factor beta- activated kinase 1 (TAK1), a potential therapeutic target for gout. Therefore, the insight on human XO structure and TAK1 provides a clue into protein-ligand interactions and provides the basis for molecular modeling and structure-based drug design. CONCLUSION: In this review, we briefly introduce the clinical characteristics, the development of crystal, inhibitors, and crystal structure of XO and TAK1 protein.

Education system of Nepal: impacts and future perspectives of COVID-19 pandemic.

The academic sectors are badly affected by the COVID-19 pandemic globally. The studies regarding the implications of COVID-19 in education in Nepal were minimal, thus, this paper aims to highlight the impacts of the pandemic on the education sector of Nepal. It is revealed that the Nepalese academia has been facing problems due to lack of adequate and appropriate sustainable infrastructure for the online system, including skilled human resources. In addition, limited internet facilities in remote and rural areas were the other challenging tasks for virtual academic activities. Therefore, the concerned stakeholders should provide necessary services and appropriate strategies for virtual means of the education system to compensate the repercussion caused by the pandemic. This study could be helpful to identify the critical needs emerged due to the pandemic at present and in future and also contribute to adopt appropriate policy for the revival of educational institutions.

Perception and Challenges of Preventive Measures of COVID-19 Among Nepalese Frontline Health Professionals: An Unexplored Realism.

Background: A new coronavirus causes COVID-19, a developing respiratory illness. Unfortunately, there is little information assessing healthcare workers' understanding of technology and preventative strategies during the Nepalese epidemic. Researchers from other subspecialties uncovered some mythical thoughts. As a result, we decided to put it to the test with healthcare personnel on the front lines. The research also looked at the problems experienced by frontline health care personnel (HCP) because of the COVID-19 strategic shift in work policy. Methods: Nepalese healthcare workers participated in web-based cross-sectional research. A pre-tested, structured questionnaire utilizing a Google form was used to get self-informed, digitally typed consent, and examine critical perspectives and problems with current technology and COVID-19 prevention efforts. Results: In total, 243 participants with mean age of 29.66 ± 7.61 years agreed to participate and were doctors (n = 27), health assistants (n = 2), medical intern doctors (n = 1), paramedical (n = 139), pharmacy (n = 1), and paramedical interns (n = 73) in this study. The calculated mean percentage score of knowledge on instruments and tools was 73.64 (SD ± 10.43) %, and perception on COVID-19 transmission and control was 70.06 (SD ± 18.30) %. At various levels, frontline health workers faced significant challenges, including the adoption of digital health technology. Conclusion: Frontline HCPs are anticipated to have updated knowledge from what the study has outlined. It is recommended to follow national guidelines. Policies should be put in place so that every frontline worker can demonstrate high standards in prevention, control, and equipment use that do not create misinformation among HCPs. Throughout, support for digital health materials and disease control methods for HCPs is essential.

New 1, 2-naphthoquinone-derived pigments from the mycobiont of lichen Trypethelium eluteriae Sprengel.

A new yellow pigment trypethelonamide A (1), and a new dark violet-red pigment 5'-hydroxytrypethelone (2), as well as three known dark violet-red pigments (+)-8-hydroxy-7-methoxytrypethelone (3), (+)-trypethelone (4) and (-)-trypethelone (5) were isolated from the cultured lichenized fungus Trypethelium eluteriae. The structures of 1 and 2 were determined to be 1, 2-naphthoquinone derivatives by extensive spectroscopic analysis. The absolute configurations of 1 and 2 were assigned by quantum electronic circular dichroism (ECD) calculation. All isolated compounds were evaluated for cytotoxicities against A549, HepG2 and RKO cell lines, and antioxidant effects on DPPH. Compounds 1-5 showed moderate and weak cytotoxicities against RKO cell line with IC50 from 22.6 to 113.5 µM.

New phenolic bisabolane sesquiterpenoid derivatives with cytotoxicity from Aspergillus tennesseensis.

Three new bisabolane sesquiterpenoid esters, aspertenols A-B (1-3), and six known compounds (4-9) were isolated from the fungus Aspergillus tennesseensis. The structures of new compounds were elucidated by extensive spectroscopic analysis. The cytotoxicities of 1-9 against A549, K562, and ASPC cell lines were tested by using the CCK8 method. Compounds 1, 3, 4, 6, 7, and 9 showed inhibition on K562 cell line with IC50 values in the range from 16.6 to 72.7 µM. Compounds 1, 4, and 9 showed moderate inhibitory activity against A549 with IC50 of 43.5, 70.2, and 61.1 µM, respectively.

Current and future perspective on antimicrobial and anti-parasitic activities of Ganoderma sp.: an update.

Medicinal mushroom Ganoderma sp. is considered to be a key source for the production of therapeutic agents. Our current review indicates that a limited number (<19%; 79 out of >430) of isolated compounds have been tested and known to be active against several microorganisms and parasites. In this review, we aim to summarise all the antimicrobial and anti-parasitic works on Ganoderma sp. displayed on web of science, google scholar and endnote X7 from 1932 to August 2016. We further present and discuss the structure of active compounds against microorganisms and parasites. In addition, we also discuss the possible further research to identify lead compounds from Ganoderma sp. as a novel strategy to combat the potential global emergence of bad bugs and parasites.