Inter-kingdom regulation of human transcriptome by dietary microRNAs: Emerging bioactives from edible plants to treat human diseases?

MicroRNAs (miRNAs) are small non-coding RNAs between 18 and 23 nts in size which regulate the translation and stability of target mRNAs. MiRNAs from dietary plants are conventionally thought to be degraded during the gastrointestinal digestion process. A few recent reports suggest that dietary microRNAs may exhibit resistance to this process, enter systemic circulation and exert biological effects on animal physiology.The horizontal transfer of miRNAs into systemic circulation is not feasible for all dietary miRNAs due to lack of bioavailability. Hence, this is a highly debated proposition with conflicting data presented in literature. Dietary miRNAs may exhibit such cross-kingdom regulation if present in extracellular vesicles which increases their bioavailability. These vesicular structures from plants are known as edible nanoparticles (ENPs). ENPs have been isolated from several edible plants. These nano-sized vesicles are filled with bioactives, proteins, lipids and miRNAs, in a bioavailable form. ENP-derived miRNAs are gaining attention due to their relative stability and resistance to degradation. ENP-derived miRNAs may enter systemic circulation and target mRNAs in recipient cells. With the COVID-19 pandemic threat worldwide, it appears that ENP-derived miRNAs could also be exploited for targeted therapeutics against SARS-CoV-2.ENP-derived miRNAs are probably more bioavailable and are spontaneously absorbed in intestinal epithelium to suppress target transcripts in human/microbial/viral kingdoms. Such cross-kingdom regulation exhibited by dietary miRNAs, if properly investigated and validated, may aid in the development of non-toxic and cost-effective therapeutics to treat human diseases.

Predictive Analysis of COVID-19 Pandemic in India Based on SIR-F Model (preprint)

Impact of COVID-19 has been devastating worldwide, it has disrupted lives of people, economy has fallen and millions of people have lost their jobs. Second peak of COVID-19 is making it even worse for many developing countries. In India, the second peak is reaching nearly 4 times the cases that were reported during the first peak, thus making it a challenge for the government to plan for the future without affecting the economy further. According to WHO, millions of enterprises are at existential threat, nearly half of the global workforce is at risk of losing their jobs and the entire food chain has been disrupted. In order to provide some assistance to the situation, this study aims to use the SIR-F Model, which is a variation of the SIR model. W. O. Kermack and A. G. McKendrick in 1927, proposed the model in which they classified a fixed population into three compartments: S(t), susceptible;I(t), Infected;R(t), Recovered. We have used the SIR-F model which differentiates between Recovered (meaning people infected and later recovered and thus now immune) and Fatality. We have simulated two scenarios including one in which we study the impact of medicine on future cases and also inspected various parameters which shed light on reasons behind increasing and decreasing the number of covid cases in India. In the future, this work can be extended further to develop a completely new model to consider those cases in which people have recovered but are still at a risk of reinfection.

A machine learning-based approach to determine infection status in recipients of BBV152 whole virion inactivated SARS-CoV-2 vaccine for serological surveys (preprint)

Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the effectiveness of interventions. Asymptomatic breakthrough infections have been a major problem during the ongoing surge of Delta variant globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines used in the higher-income regions. Here, we show for the first time how statistical and machine learning (ML) approaches can discriminate SARS-CoV-2 infection from immune response to an inactivated whole virion vaccine (BBV152, Covaxin, India), thereby permitting real-world vaccine effectiveness assessments from cohort-based serosurveys in Asia and Africa where such vaccines are commonly used. Briefly, we accessed serial data on Anti-S and Anti-NC antibody concentration values, along with age, sex, number of doses, and number of days since the last vaccine dose for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine (SVM) model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, 724 were classified as infected. Since the vaccine contains wild-type virus and the antibodies induced will neutralize wild type much better than Delta variant, we determined the relative ability of a random subset of such samples to neutralize Delta versus wild type strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, Delta variant, was neutralized more effectively than the wild type, which cannot happen without infection. The fraction rose to 71.8% (28 of 39) in subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period.

Inter-kingdom regulation of human transcriptome by dietary microRNAs: Emerging bioactives from edible plants to treat human diseases?

Abstract: Background MicroRNAs (miRNAs) are small non-coding RNAs between 18 and 23 nts in size which regulate the translation and stability of target mRNAs. MiRNAs from dietary plants are conventionally thought to be degraded during the gastrointestinal digestion process. A few recent reports suggest that dietary microRNAs may exhibit resistance to this process, enter systemic circulation and exert biological effects on animal physiology. Scope and approach The horizontal transfer of miRNAs into systemic circulation is not feasible for all dietary miRNAs due to lack of bioavailability. Hence, this is a highly debated proposition with conflicting data presented in literature. Dietary miRNAs may exhibit such cross-kingdom regulation if present in extracellular vesicles which increases their bioavailability. These vesicular structures from plants are known as edible nanoparticles (ENPs). ENPs have been isolated from several edible plants. These nano-sized vesicles are filled with bioactives, proteins, lipids and miRNAs, in a bioavailable form. ENP-derived miRNAs are gaining attention due to their relative stability and resistance to degradation. ENP-derived miRNAs may enter systemic circulation and target mRNAs in recipient cells. With the COVID-19 pandemic threat worldwide, it appears that ENP-derived miRNAs could also be exploited for targeted therapeutics against SARS-CoV-2. Key findings and conclusions ENP-derived miRNAs are probably more bioavailable and are spontaneously absorbed in intestinal epithelium to suppress target transcripts in human/microbial/viral kingdoms. Such cross-kingdom regulation exhibited by dietary miRNAs, if properly investigated and validated, may aid in the development of non-toxic and cost-effective therapeutics to treat human diseases.

Crisis aboard the aircraft carrier uss theodore roosevelt

The case details the events which happened aboard the aircraft carrier USS Theodore Roosevelt in the last weeks of March and the beginning of April of 2020. Some sailors onboard became infected by the coronavirus and there was every danger of it spreading rapidly. The Captain of the carrier was Brett Crozier, a distinguished naval officer with many years of service behind him. As his requests to get sailors off the ship was not responded to promptly, he resorted to emailing a four page letter to around 20 recipients “outside” the naval hierarchy. This was soon leaked to the press and became a major talking point. The acting Navy Secretary Thomas Modly reacted by relieving Brett Crozier of his command, stating that the latter had shown poor leadership qualities and had not followed the chain of command in communicating his problems when he had the means to do so. Crozier was a popular captain and the crew gave him a fond and touching farewell in contrast to the antagonism they showed Modly when he addressed them after the event. There was a lot of criticism about Modly’s decision making abilities which surfaced shortly after the incident and ultimately he resigned from his job. The focus of the case is on crisis management and the need for clear decision making under stressful conditions. © 2020 NeilsonJournals Publishing.

Low pH-Based Method to Increase the Yield of Plant-Derived Nanoparticles from Fresh Ginger Rhizomes.

Plant-derived nanoparticles (PDNPs) are naturally occurring exosome-like nanovesicles derived from dietary plants containing key plant bioactives. Ginger-derived PDNPs have a therapeutic effect on alcohol-induced liver injury, inflammatory bowel disease, and colon cancer. PDNPs are conventionally purified by differential ultracentrifugation, a technique not amenable for scale up. We have recently developed a polyethylene glycol (PEG) 6000-based method for cost-effective purification of ginger PDNPs, with comparable efficiency to differential ultracentrifugation (Sci. Rep. 2020, 10 (1), 4456.). Herein, we report a 4-5-fold higher ginger PDNP recovery when PEG precipitation was carried out in low pH conditions (pH 4 and 5). Low pH-derived ginger PDNPs were smaller in size without an overt change in zeta potential. The spontaneous intracellular entry and protection against oxidative stress in A431 cells were similar between ginger PDNPs purified under low, neutral, and alkaline pH. Low-pH purified ginger PDNPs had higher levels of total polyphenolic content compared to PDNPs purified under neutral and alkaline pH. Recently, ginger PDNP-derived microRNAs have been shown to exhibit cross-kingdom regulation by targeting human, gut microbiome, and viral transcripts. Using qRT-PCR, we also verified the presence of miRNAs that were predicted to target SARS-CoV-2 in ginger PDNPs purified under low pH. Thus, we have developed a method to purify ginger PDNPs in high yields by using low-pH conditions without affecting the major bioactive contents of PDNPs.

Predictive Analysis of COVID-19 Pandemic in India Based on SIR-F Model (preprint)

Impact of COVID-19 has been devastating worldwide, it has disrupted lives of people, economy has fallen and millions of people have lost their jobs. Second peak of COVID-19 is making it even worse for many developing countries. In India, the second peak is reaching nearly 4 times the cases that were reported during the first peak, thus making it a challenge for the government to plan for the future without affecting the economy further. According to WHO, millions of enterprises are at existential threat, nearly half of the global workforce is at risk of losing their jobs and the entire food chain has been disrupted. In order to provide some assistance to the situation, this study aims to use the SIR-F Model, which is a variation of the SIR model. W. O. Kermack and A. G. McKendrick in 1927, proposed the model in which they classified a fixed population into three compartments: S(t), susceptible; I(t), Infected; R(t), Recovered. We have used the SIR-F model which differentiates between Recovered (meaning people infected and later recovered and thus now immune) and Fatality. We have simulated two scenarios including one in which we study the impact of medicine on future cases and also inspected various parameters which shed light on reasons behind increasing and decreasing the number of covid cases in India. In the future, this work can be extended further to develop a completely new model to consider those cases in which people have recovered but are still at a risk of reinfection.

Exploring the disparity in global food security indicators

Much information on the food security status of countries has become increasingly available in recent years. However, alternative measures, especially with large variation, can affect policy design and delivery to alleviate food insecurity. This study explores variation within and among global food security indicators – from FAO, UNDP, IFPRI and USDA – during 1991–2018. Within variation is significantly explained by economic growth, literacy, urbanization and internet access, while a meta-regression analysis pointed to study heterogeneity as potential sources of variation among these indicators. Results have implications for future data compilation and analysis for a more accurate picture of the prevalence of undernourishment and for the effects of the ongoing pandemic on food security. © 2021 Elsevier B.V.

Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2.

To understand the spread of SARS-CoV2, in August and September 2020, the Council of Scientific and Industrial Research (India) conducted a serosurvey across its constituent laboratories and centers across India. Of 10,427 volunteers, 1058 (10.14%) tested positive for SARS-CoV2 anti-nucleocapsid (anti-NC) antibodies, 95% of which had surrogate neutralization activity. Three-fourth of these recalled no symptoms. Repeat serology tests at 3 (n = 607) and 6 (n = 175) months showed stable anti-NC antibodies but declining neutralization activity. Local seropositivity was higher in densely populated cities and was inversely correlated with a 30-day change in regional test positivity rates (TPRs). Regional seropositivity above 10% was associated with declining TPR. Personal factors associated with higher odds of seropositivity were high-exposure work (odds ratio, 95% confidence interval, p value: 2.23, 1.92-2.59, <0.0001), use of public transport (1.79, 1.43-2.24, <0.0001), not smoking (1.52, 1.16-1.99, 0.0257), non-vegetarian diet (1.67, 1.41-1.99, <0.0001), and B blood group (1.36, 1.15-1.61, 0.001).

Edible plant-derived exosomal microRNAs: Exploiting a cross-kingdom regulatory mechanism for targeting SARS-CoV-2.

BACKGROUND: The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable form. Recently, cross-kingdom regulation of human transcripts by plant miRNAs have been demonstrated. However, ENP derived miRNAs targeting SARS-CoV-2 has not been described. STUDY DESIGN: Mature ENP-derived miRNA sequences were retrieved from small RNA sequencing datasets available in the literature. In silico target prediction was performed to identify miRNAs that could target SARS-CoV-2. ENPs were isolated from ginger and grapefruit plants and the expression of SARS-CoV-2 targeting miRNAs were confirmed by qRT-PCR. RESULTS: From a total of 260 ENP-derived miRNAs, we identified 22 miRNAs that could potentially target SARS-CoV-2 genome. 11 miRNAs showed absolute target specificity towards SARS-CoV-2 but not SARS-CoV. ENPs from soybean, ginger, hamimelon, grapefruit, tomato and pear possess multiple miRNAs targeting different regions within SARS-CoV-2. Interestingly, osa/cme miR-530b-5p specifically targeted the ribosomal slippage site between ORF1a and ORF1b. We validated the relative expression of six miRNAs (miR-5077, miR-6300, miR-156a, miR-169, miR-5059 and miR-166 m) in ginger and grapefruit ENPs by RT-PCR which showed differential enrichment of specific miRNAs in ginger and grapefruit ENPs. CONCLUSION: Since administration of ENPs leads to their accumulation into lung tissues in vivo, ENP derived miRNAs targeting SARS-CoV-2 genome has the potential to be developed as an alternative therapy.

Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2 (preprint)

BackgroundIndia has been amongst the most affected nations during the SARS-CoV2 pandemic, with sparse data on country-wide spread of asymptomatic infections and antibody persistence. This longitudinal cohort study was aimed to evaluate SARS-CoV2 sero-positivity rate as a marker of infection and evaluate temporal persistence of antibodies with neutralization capability and to infer possible risk factors for infection. MethodsCouncil of Scientific and Industrial Research, India (CSIR) with its more than 40 laboratories and centers in urban and semi-urban settings spread across the country piloted the pan country surveillance. 10427 adult individuals working in CSIR laboratories and their family members based on voluntary participation were assessed for antibody presence and stability was analyzed over 6 months utilizing qualitative Elecsys SARS CoV2 specific antibody kit and GENScript cPass SARS-CoV2 Neutralization Antibody Detection Kit. Along with demographic information, possible risk factors were evaluated through self to be filled online forms with data acquired on blood group type, occupation type, addiction and habits including smoking and alcohol, diet preferences, medical history and transport type utilized. Symptom history and information on possible contact and compliance with COVID 19 universal precautions was also obtained. Findings1058 individuals (10{middle dot}14%) had antibodies against SARS-CoV2. A follow-up on 346 sero-positive individuals after three months revealed stable to higher antibody levels against SARS-CoV2 but declining plasma activity for neutralizing SARS-CoV2 receptor binding domain and ACE2 interaction. A repeat sampling of 35 individuals, at six months, revealed declining antibody levels while the neutralizing activity remained stable compared to three months. Majority of sero-positive individuals (75%) did not recall even one of nine symptoms since March 2020. Fever was the most common symptom with one-fourth reporting loss of taste or smell. Significantly associated risks for sero-positivity (Odds Ratio, 95% CI, p value) were observed with usage of public transport (1{middle dot}79, 1{middle dot}43 - 2{middle dot}24, 2{middle dot}81561E-06), occupational responsibilities such as security, housekeeping personnel etc. (2{middle dot}23, 1{middle dot}92 - 2{middle dot}59, 6{middle dot}43969E-26), non-smokers (1{middle dot}52, 1{middle dot}16 - 1{middle dot}99, 0{middle dot}02) and non-vegetarianism (1{middle dot}67, 1{middle dot}41 - 1{middle dot}99, 3{middle dot}03821E-08). An iterative regression analysis was confirmatory and led to only modest changes to estimates. Predilections for sero-positivity was noted with specific ABO blood groups -O was associated with a lower risk. InterpretationIn a first-of-its-kind study from India, we report the sero-positivity in a country-wide cohort and identify variable susceptible associations for contacting infection. Serology and Neutralizing Antibody response provides much-sought-for general insights on the immune response to the virus among Indians and will be an important resource for designing vaccination strategies. FundingCouncil of Scientific and Industrial Research, India (CSIR)