Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of activities. The combination of different pharmacophores in a pyrrole ring system has led to the formation ...of more active compounds. Pyrrole containing analogs are considered as a potential source of biologically active compounds that contains a significant set of advantageous properties and can be found in many natural products. The marketed drugs containing a pyrrole ring system are known to have many biological properties such as antipsychotic, β-adrenergic antagonist, anxiolytic, anticancer (leukemia, lymphoma and myelofibrosis
etc.
), antibacterial, antifungal, antiprotozoal, antimalarial and many more. Due to the diversity of these analogs in the therapeutic response profile, many researchers have been working to explore this skeleton to its maximum potential against several diseases or disorders. In this review, attempts have been made to disclose various tactical approaches to synthesize pyrrole and pyrrole containing analogs. The structure-activity relationship studies have been discussed along with their therapeutic applications which have been reported during last decade. Some molecules as the main components of the market and clinical trials have also been discussed.
Pyrrole is widely known as a biologically active scaffold which possesses a diverse nature of activities.
Soil salinization affecting different crops is one of the serious threats to global food security. Soil salinity affects 20% and 33% of the total cultivated and irrigated agricultural lands, ...respectively, and has been reported to caused a global crop production loss of 27.3 billion USD. The conventional approaches, such as using salt-tolerant varieties, saline soil scrapping, flushing, leaching, and adding supplements (e.g., gypsum and lime), often fail to alleviate stress. In this context, developing diverse arrays of microbes enhancing crop productivity under saline soil conditions without harming soil health is necessary. Various advanced omics approaches have enabled gaining new insights into the structure and metabolic functions of plant-associated beneficial microbes. Various genera of salt-tolerating rhizobacteria ameliorating biotic and abiotic stresses have been isolated from different legumes, cereals, vegetables, and oil seeds under extreme alkaline and saline soil conditions. Rapid progress in rhizosphere microbiome research has revived the belief that plants may be more benefited from their association with interacting diverse microbial communities as compared with individual members in a community. In the last decade, several salt-tolerating plant growth-promoting rhizobacteria (PGPR) that improve crop production under salt stress have been exploited for the reclamation of saline agrosystems. This review highlights that the interaction of salt-tolerating microbes with plants improves crop productivity under salinity stress along with potential salt tolerance mechanisms involved and will open new avenues for capitalizing on cultivable diverse microbial communities to strengthen plant salt tolerance and, thus, to refine agricultural practices and production under saline conditions.
In this paper, we have demonstrated and designed a 2D photonic crystal-based biosensor with line defect, which can detect glucose concentration in urine. Simulation and analysis have been done in ...order to detect glucose concentration in normal urine (0-15 mg/dL), urine with 0.625, 1.25, 2.5, 5, and 10 gm/dL of glucose concentration in the wavelength range of 1530-1565 nm. Finite-difference time-domain method has been used for the analysis. Massachusetts Institute of Technology electromagnetic equation propagation and MIT photonic bands simulation tools have been used for modeling and designing of photonic crystal, and IPKISS software framework has been used for generation of mask design, which can be used for the fabrication of the photonic crystal sensor. It has been observed from the band structure that for little change in refractive index, there will be a moderate shift in the frequency and transmitted output power and hence it acts as a sensor. This indicates that it is highly sensitive for the change in refractive index.
•Biorefinery and bioprocessing are sustainable ways for resource conservation.•Circular bioeconomy significantly reduces food waste accumulation.•In depth studies are necessary to close knowledge ...gaps in field of food waste valorization.•The major stumbling block in resource recovery from food waste is cost of production.
Sustainable development of circular bioeconomy concept is only possible upon adopting potential advanced technologies for food waste valorization. This approach can simultaneously answer resources and environmental challenges incurred due to capital loss and greenhouse gases accumulation. Food waste valorization opens new horizons of economical growth, bringing waste as an opportunity feedstock for bio processes to synthesize biobased products from biological source in a circular loop. Advanced technologies like Ultrasound assisted extraction, Microwave assisted extraction, bioreactors, enzyme immobilization assisted extraction and their combination mitigates the global concern caused due to mismanagement of food waste. Food waste decomposition to sub-zero level using advanced techniques fabricates food waste into bio-based products like bioactive compounds (antioxidants, pigments, polysaccharides, polyphenols, etc.); biofuels (biodiesel, biomethane, biohydrogen); and bioplastics. This review abridges merits and demerits of various advanced techniques extended for food waste valorization and contribution of food waste in revenue generation as value added products.
Probiotics are known to have a long history of safe use and can be formulated into many different types of products, including foods, drugs, and dietary supplements. Several probiotic microorganisms ...like genus Lactococcus, Lactobacillus, Streptococcus, Enterococcus, Bifidobacterium, Pediococcus and Propionibacteria spp. are these days used in fermented dairy products and drug formulations. Due to their human consumption, safety of these organisms is of primary importance as their resistance towards antibiotics can be one of the possible threat. The gravity of this issue is further compounded by the possibility of bacteria to transfer resistance determinants horizontally to pathogens and commensal gut microbiota. Antibiotic resistance in these beneficial microbes, either intrinsic or due to any mutation does not manifest a safety concern in itself. Some probiotic strains with intrinsic antibiotic resistance per se could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, have often been detected in the typical probiotic genera, and hence constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue. Plasmid-associated antibiotic resistance, which occasionally occurs, is a matter of concern as it can be detrimental to use of probiotics owing the possibility of the resistance spreading to harmful microorganisms inhabiting the same niche. Further, the presence of transferable antibiotic resistance genes even to a less innocuous member of the gut microbial community poses a safety hazard and needs to be taken into account. Probiotic safety is beleaguered with the scarcity of well designed and targeted studies and needs to be dealt in right perspective. This review aims to deliberate on the presence of antibiotic resistance in commercially used probiotic organisms and their potential transfer to pathogens and other commensal microbiota present in the gut.
•Antibiotic resistance is a burning issue worldwide.•Probiotics can act as a mode of resistance transfer to pathogens.•Complete review of antibiotic resistance reported in commercial probiotics
Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has caused a pandemic of historic proportions and continues to spread globally, with enormous consequences to human health. ...Currently there is no vaccine, effective therapeutic, or prophylactic. As with other betacoronaviruses, attachment and entry of SARS-CoV-2 are mediated by the spike glycoprotein (SGP). In addition to its well-documented interaction with its receptor, human angiotensin-converting enzyme 2 (hACE2), SGP has been found to bind to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we pseudotyped SARS-CoV-2 SGP on a third-generation lentiviral (pLV) vector and tested the impact of various sulfated polysaccharides on transduction efficiency in mammalian cells. The pLV vector pseudotyped SGP efficiently and produced high titers on HEK293T cells. Various sulfated polysaccharides potently neutralized pLV-S pseudotyped virus with clear structure-based differences in antiviral activity and affinity to SGP. Concentration-response curves showed that pLV-S particles were efficiently neutralized by a range of concentrations of unfractionated heparin (UFH), enoxaparin, 6-
-desulfated UFH, and 6-
-desulfated enoxaparin with 50% inhibitory concentrations (IC
s) of 5.99 μg/liter, 1.08 mg/liter, 1.77 μg/liter, and 5.86 mg/liter, respectively. In summary, several sulfated polysaccharides show potent anti-SARS-CoV-2 activity and can be developed for prophylactic as well as therapeutic purposes.
The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, in late 2019 and its subsequent spread to the rest of the world has created a pandemic situation unprecedented in modern history. While ACE2 has been identified as the viral receptor, cellular polysaccharides have also been implicated in virus entry. The SARS-CoV-2 spike glycoprotein (SGP) binds to glycosaminoglycans like heparan sulfate, which is found on the surface of virtually all mammalian cells. Here, we report structure-based differences in antiviral activity and affinity to SGP for several sulfated polysaccharides, including both well-characterized FDA-approved drugs and novel marine sulfated polysaccharides, which can be developed for prophylactic as well as therapeutic purposes.
CD4
Foxp3
regulatory T cells (Tregs) protect the kidney during AKI. We previously found that IL-2, which is critical for Treg homeostasis, upregulates the IL-33 receptor (ST2) on CD4
T cells, thus we ...hypothesized that IL-2 and IL-33 cooperate to enhance Treg function. We found that a major subset of Tregs in mice express ST2, and coinjection of IL-2 and IL-33 increased the number of Tregs in lymphoid organs and protected mice from ischemia-reperfusion injury (IRI) more efficiently than either cytokine alone. Accordingly, we generated a novel hybrid cytokine (IL233) bearing the activities of IL-2 and IL-33 for efficient targeting to Tregs. IL233 treatment increased the number of Tregs in blood and spleen and prevented IRI more efficiently than a mixture of IL-2 and IL-33. Injection of IL233 also increased the numbers of Tregs in renal compartments. Moreover, IL233-treated mice had fewer splenic Tregs and more Tregs in kidneys after IRI.
, splenic Tregs from IL233-treated mice suppressed CD4
T cell proliferation better than Tregs from saline-treated controls. IL233 treatment also improved the ability of isolated Tregs to inhibit IRI in adoptive transfer experiments and protected mice from cisplatin- and doxorubicin-induced nephrotoxic injury. Finally, treatment with IL233 increased the proportion of ST2-bearing innate lymphoid cells (ILC2) in blood and kidneys, and adoptive transfer of ILC2 also protected mice from IRI. Thus, the novel IL233 hybrid cytokine, which utilizes the cooperation of IL-2 and IL-33 to enhance Treg- and ILC2-mediated protection from AKI, bears strong therapeutic potential.
Biosurfactants are the chemical compounds that are obtained from various micro-organisms and possess the ability to decrease the interfacial tension between two similar or different phases. The ...importance of biosurfactants in cosmetics, pharmaceuticals, biotechnology, agriculture, food and oil industries has made them an interesting choice in various physico-chemical and biological applications. With the aim of representing different properties of biosurfactants, this review article is focused on emphasizing their applications in various industries summarizing their importance in each field. Along with this, the production of recently developed chemically and biologically important biosurfactants has been outlined. The advantages of biosurfactants over the chemical surfactants have also been discussed with emphasis on the latest findings and research performed worldwide. Moreover, the chemical and physical properties of different biosurfactants have been presented and different characterization techniques have been discussed. Overall, the review article covers the latest developments in biosurfactants along with their physico-chemical properties and applications in different fields, especially in pharmaceuticals and biotechnology.
Biosurfactants; Microbes; Applications; Biotechnology; Pharmaceuticals.
Heart disease causing cardiac cell death due to ischemia–reperfusion injury is a major cause of morbidity and mortality in the United States. Coronary heart disease and cardiomyopathies are the major ...cause for congestive heart failure, and thrombosis of the coronary arteries is the most common cause of myocardial infarction. Cardiac injury is followed by post-injury cardiac remodeling or fibrosis. Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium and results in both systolic and diastolic dysfunctions. It has been suggested by both experimental and clinical evidence that fibrotic changes in the heart are reversible. Hence, it is vital to understand the mechanism involved in the initiation, progression, and resolution of cardiac fibrosis to design anti-fibrotic treatment modalities. Animal models are of great importance for cardiovascular research studies. With the developing research field, the choice of selecting an animal model for the proposed research study is crucial for its outcome and translational purpose. Compared to large animal models for cardiac research, the mouse model is preferred by many investigators because of genetic manipulations and easier handling. This critical review is focused to provide insight to young researchers about the various mouse models, advantages and disadvantages, and their use in research pertaining to cardiac fibrosis and hypertrophy.
Obesity-linked (type 2) diabetic nephropathy (T2DN) has become the largest contributor to morbidity and mortality in the modern world. Recent evidences suggest that inflammation may contribute to the ...pathogenesis of T2DN and T-regulatory cells (Treg) are protective. We developed a novel cytokine (named IL233) bearing IL-2 and IL-33 activities in a single molecule and demonstrated that IL233 promotes Treg and T-helper (Th) 2 immune responses to protect mice from inflammatory acute kidney injury. Here, we investigated whether through a similar enhancement of Treg and inhibition of inflammation, IL233 protects from T2DN in a genetically obese mouse model, when administered either early or late after the onset of diabetes. In the older mice with obesity and microalbuminuria, IL233 treatment reduced hyperglycemia, plasma glycated proteins, and albuminuria. Interestingly, IL233 administered before the onset of microalbuminuria not only strongly inhibited the progression of T2DN and reversed diabetes as indicated by lowering of blood glucose, normalization of glucose tolerance and insulin levels in islets, but surprisingly, also attenuated weight gain and adipogenicity despite comparable food intake. Histological examination of kidneys showed that saline control mice had severe inflammation, glomerular hypertrophy, and mesangial expansion, which were all attenuated in the IL233 treated mice. The protection correlated with greater accumulation of Tregs, group 2 innate lymphoid cells (ILC2), alternately activated macrophages and eosinophils in the adipose tissue, along with a skewing toward T-helper 2 responses. Thus, the novel IL233 cytokine bears therapeutic potential as it protects genetically obese mice from T2DN by regulating multiple contributors to pathogenesis.
A novel bifunctional cytokine IL233, bearing IL-2 and IL-33 activities reverses inflammation and protects from type-2 diabetic nephropathy through promoting T-regulatory cells and type 2 immune response.
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