Current perspective in research and industrial applications of microbial cellulases.

The natural interactions between various bacteria, fungi, and other cellulolytic microorganisms destroy lignocellulosic polymers. The efficacy of this process is determined by the combined action of three main enzymes: endoglucanases, exo-glucanases, and ß-glucosidase. The enzyme attacks the polymeric structure's ß-1,4-linkages during the cellulose breakdown reaction. This mechanism is crucial for the environment as it recycles cellulose in the biosphere. However, there are problems with enzymatic cellulose breakdown, including complex cellulase structure, insufficient degradation efficacy, high production costs, and post-translational alterations, many of which are closely related to certain unidentified cellulase properties. These issues impede the practical use of cellulases. A developing area of research is the application of this similar paradigm for industrial objectives. Cellulase enzyme exhibits greater promise in many critical industries, including biofuel manufacture, textile smoothing and finishing, paper and pulp manufacturing, and farming. However, the study on cellulolytic enzymes must move forward in various directions, including increasing the activity of cellulase as well as designing peptides to give biocatalysts their desired attributes. This manuscript includes an overview of current research on different sources of cellulases, their production, and biochemical characterization.

Understanding gut microbiome-based machine learning platforms: A review on therapeutic approaches using deep learning.

Human beings possess trillions of microbial cells in a symbiotic relationship. This relationship benefits both partners for a long time. The gut microbiota helps in many bodily functions from harvesting energy from digested food to strengthening biochemical barriers of the gut and intestine. But the changes in microbiota composition and bacteria that can enter the gastrointestinal tract can cause infection. Several approaches like culture-independent techniques such as high-throughput and meta-omics projects targeting 16S ribosomal RNA (rRNA) sequencing are popular methods to investigate the composition of the human gastrointestinal tract microbiota and taxonomically characterizing microbial communities. The microbiota conformation and diversity should be provided by whole-genome shotgun metagenomic sequencing of site-specific community DNA associating genome mapping, gene inventory, and metabolic remodelling and reformation, to ease the functional study of human microbiota. Preliminary examination of the therapeutic potency for dysbiosis-associated diseases permits investigation of pharmacokinetic-pharmacodynamic changes in microbial communities for escalation of treatment and dosage plan. Gut microbiome study is an integration of metagenomics which has influenced the field in the last two decades. And the incorporation of artificial intelligence and deep learning through "omics-based" methods and microfluidic evaluation enhanced the capability of identification of thousands of microbes.

Antibiotic-Induced Biofilm Formations in Pseudomonas aeruginosa Strains KPW.1-S1 and HRW.1-S3 are Associated with Increased Production of eDNA and Exoproteins, Increased ROS Generation, and Increased Cell Surface Hydrophobicity.

Pseudomonas aeruginosa is a medically important opportunistic pathogen due to its intrinsic ability to form biofilms on different surfaces as one of the defense mechanisms for survival. The fact that it can form biofilms on various medical implants makes it more harmful clinically. Although various antibiotics are used to treat Pseudomonas aeruginosa infections, studies have shown that sub-MIC levels of antibiotics could induce Pseudomonas biofilm formation. The present study thus explored the effect of the aminoglycoside antibiotic gentamicin on the biofilm dynamics of two Pseudomonas aeruginosa strains KPW.1-S1 and HRW.1-S3. Biofilm formation was found to be increased in the presence of increased concentrations of gentamicin. Confocal, scanning electron microscopy, and other biochemical tests deduced that biofilm-forming components exoproteins, eDNA, and exolipids as exopolymeric substances in Pseudomonas aeruginosa biofilms were increased in the presence of gentamicin. An increase in reactive oxygen species generation along with increased cell surface hydrophobicity was also seen for both strains when treated with gentamicin. The observed increase in the adherence of the cells accompanied by the increase in the components of exopolymeric substances may have largely contributed to the increased biofilm production by the Pseudomonas aeruginosa strains under the stress of the antibiotic treatment.

Diets, Lifestyles and Metabolic Risk Factors among Corporate Information Technology (IT) Employees in South India.

(1) Information Technology (IT) Business Process Outsourcing (BPO), the largest employment sector of India, contributes to rapid economic growth. However, the work of IT employees is sedentary, and the food environments of their worksites expose them to an obesogenic environment. This study aimed to assess their metabolic and lifestyle risk factors. (2) Methods: To examine the health and nutrition status of IT employees, anthropometric, biochemical and clinical assessments were conducted among 183 employees from three IT organizations of varied operational sizes. Their health-, diet- and physical activity-related practices were assessed using a questionnaire. The prevalence of MetS was assessed. Selected biomarker levels were assessed and associated with their self-perceived stress levels. (3) Results: The median age of the employees was 30 years (26-35 years). While 44.02% of employees were overweight, 16.85% of employees were obese. About 3.89% of employees were found to be diabetic, and HDL-C levels were lower than recommended in 64.93% of employees. In all, 29.87% of the study population were considered to have metabolic syndrome since they had metabolic risk scores ≥ 3. Those with metabolic syndrome were significantly older (p = 0.000), and levels of MDA (p = 0.003), homocysteine (p = 0.001), IL-6 (p = 0.017) and IL-4 (p = 0.000) were significantly higher among them. Although the prevalence of MetS was significantly lower among those aged >30 years, the lifestyle risk factors were significantly higher among them. (4) Conclusions: The assessed parameters indicate a high risk of developing NCDs among employees in the IT industry in India. This shows the need for the modification of lifestyle and workplace food and physical activity environments.

Pharmacophore based virtual screening & molecular docking approach for identification of mycobacterial membrane protein large 3 (MmpL3) inhibitors.

Tuberculosis (TB) disease continues to remain one of the global threats for mankind. Till date many antibacterial compounds have been identified to target mycobacterium tuberculosis (MTB). However, the mutating nature of the mycobacteria has always posed a challenge for designing newer drugs which can target both the non-mutating and mutating forms of TB. In this process, Mycobacterial membrane protein Large 3 (MmpL3) transporter was identified as one of the key targets for inhibiting tuberculosis. Herein we have made an effort to find potential inhibitors against MmpL3 by using a pharmacophore-based virtual screening workflow, followed by molecular docking studies and molecular dynamic simulations. Based on a set of 220 compounds showing anti-tubercular activity proposed to target MmpL3 transporter with MIC values ranging from 0.003 to 737 µM, a 5-point pharmacophore ADHHR_2 model possessing one hydrogen acceptor, one hydrogen donor, two hydrophobic groups and an aromatic ring system was generated. The model validated by enrichment study was used to screen Asinex and DrugBank database to identify a potential lead compound such as DrugBank_6059 that was found to show better binding affinity (-11.36) and hydrophobic interactions with target protein in comparison to standard drug SQ109.Communicated by Ramaswamy H. Sarma.

Identifying opportunities and barriers for introducing a workplace nutrition and health program for employees: Findings from formative research.

BACKGROUND: The work style of employees engaged in the Information Technology (IT) and Business Process Outsourcing (BPO) sectors in India is dominantly sedentary exposing them to detrimental obesogenic environments with unhealthy diets, increasing the risk of non-communicable diseases (NCDs). Workplace health interventions have been reported to have the potential of reducing NCDs and related risk factors among the employees and thus reduce cost of absenteeism and improve productivity. OBJECTIVE: This formative research study aims to explore the opportunities and barriers of the development and implementation of a Workplace Health Programme (WHP). METHODS: In this study, a mixed method including qualitative and quantitative approaches were used. Focus group discussions (FGDs) were conducted with employees and senior managers in employers of IT/BPO companies of different sizes in Hyderabad, India. The food and physical activity environment in the workplaces were explored using a checklist and ground truthing approach. A knowledge, attitudes and practices (KAP) questionnaire was developed to assess health, nutrition and physical activity of the employees. RESULTS: Through this formative research, the required areas for nutrition, physical activity and health education were identified. The scope of utilising existing facilities for physical activity and modifying the food environment was explored. We noted optimistic bias among the junior employees who did not consider themselves at risk of developing NCDs. CONCLUSIONS: The identified opportunities and barriers will help in developing strategic WHPs suitable to individual workplaces. The qualitative methods, ground truthing approach, checklist and KAP tools used here can assess the company environment and employee health and nutrition status.

Impact of 'infodemic in pandemic' on food and nutrition related perceptions and practices of Indian internet users.

The uncontrolled spread of (mis)information, news and propaganda related to COVID 19 created an 'infodemic' leading to panic and unscientific practices among the mass. With the largest number of internet users in the world, India has witnessed a steep rise in the number of people seeking information on social media related to COVID-19, which reached a staggering 22.3 million by March, 2020. This study aimed to evaluate the trend of COVID-19 associated food and nutrition news search by Indian internet users between 27th January 2020 to 30th June 2021 (time period between the first detected COVID-19 case and the end of the second wave in India) and its impact on their perceptions and practices. The association between the change in Relative Search Volume (RSV) on Google Trends (GT) of 34 popularly searched keywords classified by the researchers under 5 different categories-"Immunity", "Eating behavior", "Food safety", "Food scares and concerns" and "Covid scare" showed a steep rise in search for immunity boosters, vitamin supplement brands "ayush kadha (ayurvedic decoction) during the first wave (April- August 2020). With a brief period of decline in the search trend, it again hiked correspondingly with the growing number of positive cases during the second wave in India. An online survey conducted on adult Indian internet users (n = 572) reported high (71.9%) consumption of Vitamin C rich fruits as well as Vitamin C (68.2%) and Zinc (61.4%) supplements to boost immunity. Traditional Indian spices like ginger and garlic were used by 62.9% and 50.9% respondents respectively. Most respondents reported to rely on social media for gathering COVID-19 associated tips for boosting immunity, however those with history of COVID-19 infection reported to rely more on doctors and health professionals for information. This study highlights the need of media and health literacy to advocate for the use of health information cautiously.

Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine ß-coronavirus-induced neuroinflammation.

Mouse hepatitis virus (MHV; m-ß-CoV) serves as a useful model for studying the cellular factors involved in neuroinflammation. To understand the role of matrix metalloproteinases (MMPs) in neuroinflammation, brain tissues from m-ß-CoV-infected mice were harvested at different days post-infection (d.p.i) and investigated for Mmp expression by RT-qPCR. Mmp-2, -3, -8, -12 showed significant mRNA upregulation peaking with viral replication between 5 and 6 d.p.i. Elevated levels of MMP regulator TIMP-1 are suggestive of a TIMP-1 mediated host antiviral response. Biological network assessment suggested a direct involvement of MMP-3, -8, -14 in facilitating peripheral leukocyte infiltrations. Flow cytometry confirmed the increased presence of NK cells, CD4+ and CD8+ T cells, neutrophils, and MHCII expressing cells in the m-ß-CoV infected mice brain. Our study revealed that m-ß-CoV upregulated Park7, RelA, Nrf2, and Hmox1 transcripts involved in ROS production and antioxidant pathways, describing the possible nexus between oxidative pathways, MMPs, and TIMP in m-ß-CoV-induced neuroinflammation.

Marine natural products as source of new drugs: an updated patent review (July 2018-July 2021).

INTRODUCTION: Marine natural products have aided as rich sources of new bioactive agents. The multiplicity of marine habitations and exclusive ecological conditions of the sea offer mostly unexploited sources of unique biological and chemical entities. In continuation with the authors' previous publication, the present study reviews recently published patents in correlation to the efforts in finding new therapeutically potent chemical and biological entities from marine organisms. AREAS COVERED: This review summarizes the progress in the field of marine natural products as therapeutic agents based on an analysis of the patents published after June 2018. We have identified 68 unique patent families related to novel marine natural products for this time period. Patent information pertaining to therapeutic applications and clinical studies has been analyzed and reported. EXPERT OPINION: Marine organisms are excellent producers of secondary metabolites with diverse structures and pharmacological activities. Cumulative increase in the number of patents published during the last few years justifies the importance of this study for spotting new entities as sources of therapeutic agents. The new compounds have been claimed to show a range of activities predominantly anticancer, antimicrobial, anti-inflammatory, and neuroprotection. Majority of the recent patents have been filed by Chinese inventors, and a number of these patents are still in the prosecution stage.

Biochemical, molecular and in silico characterization of arsenate reductase from Bacillus thuringiensis KPWP1 tolerant to salt, arsenic and a wide range of pH.

The present study characterized aresenate reductase of Bacillus thuringiensis KPWP1, tolerant to salt, arsenate and a wide range of pH during growth. Interestingly, it was found that arsC, arsB and arsR genes involved in arsenate tolerance are distributed in the genome of strain KPWP1. The inducible arsC gene was cloned, expressed and the purified ArsC protein showed profound enzyme activity with the KM and Kcat values as 25 µM and 0.00119 s-1, respectively. In silico studies revealed that in spite of 19-26% differences in gene sequences, the ArsC proteins of Bacillus thuringiensis, Bacillus subtilis and Bacillus cereus are structurally conserved and ArsC structure of strain KPWP1 is close to nature. Docking and analysis of the binding site showed that arsenate ion interacts with three cysteine residues of ArsC and predicts that the ArsC from B. thuringiensis KPWP1 reduces arsenate by using the triple Cys redox relay mechanism.

Ferroportin-inhibitor salt: patent evaluation WO2018192973.

INTRODUCTION: Iron is a crucial element necessary for blood formation in the body and its normal growth. However, irregular metabolism of iron due to absence of an elimination mechanism may deposit excess iron in the organs (iron overload) leading to metabolic disorders. Interactions between the iron regulatory peptide hormone, hepcidin and the iron exporter ferroportin plays major role in regulating the iron metabolism. Mutations in the ferroportin encoding genes, and dysregulation of hepsidin production often results in iron overload resulting in conditions like hemochromatosis, ß-thalassemia, and sickle cell anemia. Until today, there is no efficacious treatment available for managing iron overload targeting ferroportin inhibition via oral administration. AREAS COVERED: Novel salts of substituted benzoimidazole compounds useful for the prophylaxis and/or treatment of iron overload are claimed. These compounds act as hepcidin mimetic and inhibit the ferroportin thereby preventing iron overload. The claimed actives are useful in the treatment of disease conditions such as neurodegenerative and cardiac diseases triggered by iron overload. Preclinical studies of these salts on mouse model are also discussed. EXPERT OPINION: Prevention and/or treatment of iron overload is critical. The claimed compounds are the first oral drug candidate to treat iron overload and reach the pre-clinical development stage.

ATP Synthase, an Emerging Target in TB Drug Discovery: Review of SAR and Clinical Pharmacology of Diarylquinoline Inhibitors.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (MTB) is one of the leading causes of mortality worldwide, with an estimated 1.5 million deaths annually. The majority of infection cases are reported from the Southeast Asian region, including India. After the discovery of Streptomycin in 1943 and its anti-tubercular activity in 1945, drug discovery efforts identified Isoniazid, Ethambutol, and Rifampin as TB-actives. However, over the years, these drugs have been rendered ineffective due to genetic mutations in mycobacterial strains. This has shifted drug discovery efforts towards identifying new targets and drugs for drug-resistant forms of bacteria. ATP synthase was identified as one of the key targets of MDR-TB. This review provides key insights into the ATP synthase target, structure activity relationship studies (SAR) of diarylquinoline class of inhibitors and their clinical relevance for treating MDR-TB.

Calorie counting smart phone apps: Effectiveness in nutritional awareness, lifestyle modification and weight management among young Indian adults.

Calorie counting mobile apps claim to assist in weight management by helping users monitor their diets and track activity. This study assessed quality and effectiveness of popular calorie counting apps in weight management and behaviour change. Top 20 apps were selected from Google Play store and their quality was assessed using a 55-point scoring scale on attributes like standards used, content accuracy, user interface and sources of database. The mean (±SD (standard deviation)) quality score was 36.95 (±5.65). The calorie and activity recommendations were compared with standards and over 65 per cent apps over/underestimated calorie intake. To assess effectiveness, 60 young volunteers were recruited and divided into two groups. The intervention group (n = 30) was asked to use one of the top 3 apps for 8 weeks. Pre- and post-comparisons were made with the control group (n = 28). No significant difference was noted in anthropometry or food consumption. There was increasing trend (13.33%) in physical activity in the intervention group.

Marine natural products as source of new drugs: a patent review (2015-2018).

INTRODUCTION: Natural products from plants, animals, microbes, and minerals have long been a traditional source for the treatment of human diseases. In the past decades, research on natural products for the pharmaceutical industry had declined due to numerous challenges. However, the recent developments in analytical technology, spectroscopy, and high-throughput screening have tremendously revived natural product drug discovery, including contribution from marine-based drugs. The marine environment is a unique resource enclosing a massive biological diversity, which if genuinely explored might potentially lead to breakthrough therapies. A growing number of compounds from marine sources are entering clinical trials and thus, the impact of this field on the pharmaceutical industry is increasing. AREAS COVERED: This review summarizes the progress in the field of marine natural products as therapeutic agents based on an analysis of the patents published in the period January 2015 through June 2018. EXPERT OPINION: Marine organisms are excellent producers of natural chemicals with diverse structures and pharmacological activities. Cumulative increase in the number of patents published in the last few years clearly justifies the importance of these chemicals as sources of new therapeutic agents and this study. Despite the critical supply challenges, marine-derived actives are being explored as sources for anticancer, antimicrobial, antiviral and anti-inflammatory drugs and treatments for several other conditions.

Therapeutic use of colchicine and its derivatives: a patent review.

INTRODUCTION: Colchicine, the major alkaloid extracted from the meadow saffron (Colchicum autumnale) is one of the most prominent natural products belonging to the class of organic compounds known as tropones. Colchicine's medicinal properties have been long-known, but it has been attracting renewed attention due to its action as an antimitotic agent. Areas covered: This review presents an update and analysis of the patents claiming therapeutic activity of colchicine and its derivatives published in the last five years (2010-2015). Other patents claiming the application of colchicine in the areas of biotechnology, veterinary, and agriculture are therefore excluded from this review. Expert opinion: Rapid increase in the number of publications and patent filings in recent years for the significant therapeutic potential of colchicine, for several conditions beyond gout, clearly indicates the growing interest of research on this molecule. Although the molecular structure of colchicine fulfils the four Lipinski's requisites for high oral bioavailability, the toxic side effects resulting from its fast metabolism need to be assessed. Further efforts are therefore required to explore the appropriate dosage and possible administration techniques of colchicine for practical use.

'Click chemistry' for diagnosis: a patent review on exploitation of its emerging trends.

INTRODUCTION: Click chemistry is the novel synthetic approach towards developing reactions with large thermodynamic driving forces to give almost complete conversion of new molecular reagents to a single product. Thus, click chemistry describes the chemistry for making carbon-heteroatom-carbon bonds in benign solvents, especially in water, and having a plethora of chemical and biological applications. This has played an important role in early detection of diseases, real-time monitoring of drug delivery and investigating the biomolecular functions in vivo. AREAS COVERED: This review aims at highlighting the research advancements in click chemistry published in the patent literature and categorizing the patents according to the technological progress. An extensive search was carried out to collect and analyze the patent information claiming the use of click chemistry in biotechnology, especially for diagnosis. The study further concentrates on licensing of the click chemistry patents and defining the recent breakthroughs. Different databases like Espacenet, ISI Web of Science, Patbase and Thomson Innovation are used to compile the relevant literature. EXPERT OPINION: In recent years, considerable development in the click concept has encouraged researchers in using click reactions in almost every branch of industry that uses chemistry. Click chemistry for chemical ligation has been immensely explored in the field of biotechnology especially for detection, diagnosis and therapeutics.

Modifying lipid rafts promotes regeneration and functional recovery.

Ideal strategies to ameliorate CNS damage should promote both neuronal survival and axon regeneration. The receptor Neogenin promotes neuronal apoptosis. Its ligand prevents death, but the resulting repulsive guidance molecule a (RGMa)-Neogenin interaction also inhibits axonal growth, countering any prosurvival benefits. Here, we explore strategies to inhibit Neogenin, thus simultaneously enhancing survival and regeneration. We show that bone morphogenetic protein (BMP) and RGMa-dependent recruitment of Neogenin into lipid rafts requires an interaction between RGMa and Neogenin subdomains. RGMa or Neogenin peptides that prevent this interaction, BMP inhibition by Noggin, or reduction of membrane cholesterol all block Neogenin raft localization, promote axon outgrowth, and prevent neuronal apoptosis. Blocking Neogenin raft association influences axonal pathfinding, enhances survival in the developing CNS, and promotes survival and regeneration in the injured adult optic nerve and spinal cord. Moreover, lowering cholesterol disrupts rafts and restores locomotor function after spinal cord injury. These data reveal a unified strategy to promote both survival and regeneration in the CNS.

Probing the fractal pattern and organization of Bacillus thuringiensis bacteria colonies growing under different conditions using quantitative spectral light scattering polarimetry.

Development of methods for quantification of cellular association and patterns in growing bacterial colony is of considerable current interest, not only to help understand multicellular behavior of a bacterial species but also to facilitate detection and identification of a bacterial species in a given space and under a given set of condition(s). We have explored quantitative spectral light scattering polarimetry for probing the morphological and structural changes taking place during colony formations of growing Bacillus thuringiensis bacteria under different conditions (in normal nutrient agar representing favorable growth environment, in the presence of 1% glucose as an additional nutrient, and 3 mM sodium arsenate as toxic material). The method is based on the measurement of spectral 3×3 Mueller matrices (which involves linear polarization measurements alone) and its subsequent analysis via polar decomposition to extract the intrinsic polarization parameters. Moreover, the fractal micro-optical parameter, namely, the Hurst exponent H, is determined via fractal-Born approximation-based inverse analysis of the polarization-preserving component of the light scattering spectra. Interesting differences are noted in the derived values for the H parameter and the intrinsic polarization parameters (linear diattenuation d, linear retardance δ, and linear depolarization Δ coefficients) of the growing bacterial colonies under different conditions. The bacterial colony growing in presence of 1% glucose exhibit the strongest fractality (lowest value of H), whereas that growing in presence of 3 mM sodium arsenate showed the weakest fractality. Moreover, the values for δ and d parameters are found to be considerably higher for the colony growing in presence of glucose, indicating more structured growth pattern. These findings are corroborated further with optical microscopic studies conducted on the same samples.

Glucose induced fractal colony pattern of Bacillus thuringiensis.

Growing colonies of bacteria on the surface of thin agar plates exhibit fractal patterns as a result of nonlinear response to environmental conditions, such as nutrients, solidity of the agar medium and temperature. Here, we examine the effect of glucose on pattern formation by growing colonies of Bacillus thuringiensis isolate KPWP1. We also present the theoretical modeling of the colony growth of KPWP1 and the associated spatio-temporal patterns. Our experimental results are in excellent agreement with simulations based on a reaction-diffusion model that describes diffusion-limited aggregation and branching, in which individual cells move actively in the periphery, but become immotile in the inner regions of the growing colony. We obtain the Hausdorff fractal dimension of the colony patterns: D(H.Expt)=1.1969 and D(H, R.D.=)1.1965, for experiment and reaction-diffusion model, respectively. Results of our experiments and modeling clearly show how glucose at higher concentration can prove to be inhibitory for motility of growing colonies of B. thuringiensis cells on semisolid support and be responsible for changes in the growth pattern.