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The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure–activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

Stilbene and benzofuran derivatives isolated from the root of white mulberry ( Morus alba ) have shown various biological activities, including anti-inflammatory, antioxidant, and antimicrobial properties. The objectives of this study were to develop hairy root cultures and assess the effect of multiple elicitors combinations including (I) methyl-β-cyclodextrin (CD), MgCl 2 , methyl jasmonate (MeJA), and H 2 O 2 , (II) CD, MgCl 2 , and MeJA and (III) CD, MgCl 2, and H 2 O 2 , on the production of these bioactive compounds. The highest yields of stilbenes and benzofurans were obtained upon co-treatment with 18 g/L CD, 3 mM H 2 O 2 and 1 mM MgCl 2 . The stilbenes oxyresveratrol, resveratrol, and 3'-prenylresveratrol accumulated up to 6.27, 0.61, and 5.00 mg/g DW root, respectively. Meanwhile, the aryl benzofurans moracin M and moracin C accumulated up to 7.82 and 1.82 mg/g DW root, respectively. These stilbenes and benzofurans accumulated in the culture medium of the elicited hairy root cultures. They were not detected in the root tissue. However, the oxyresveratrol diglucoside mulberroside A was only detected in the root tissue with yields up to 10.01 mg/g DW. The results demonstrated that co-treatment of white mulberry hairy root cultures with multiple elicitors can significantly enhance production and secretion of stilbenes and benzofurans in this controlled and sustainable axenic culture system.

Pattern recognition plays a critical role in integrative bioinformatics to determine the structural patterns of proteins of viruses such as SARS-CoV-2. This study identifies the pattern of SARS-CoV-2 proteins to depict the structure-function relationships of the protein alphabets of SARS-CoV-2 and COVID-19. The assembly enumeration algorithm, Anisotropic Network Model, Gaussian Network Model, Markovian Stochastic Model, and image comparison protein-like alphabets were used. The distance score was the lowest with 22 for "I" and highest with 40 for "9". For post-processing and decision, two protein alphabets "C" (PDB ID: 6XC3) and "S" (PDB ID: 7OYG) were evaluated to understand the structural, functional, and evolutionary relationships, and we found uniqueness in the functionality of proteins. Here, models were constructed using "SARS-CoV-2 proteins" (12 numbers) and "non-SARS-CoV-2 proteins" (14 numbers) to create two words, "SARS-CoV-2" and "COVID-19". Similarly, we developed two slogans: "Vaccinate the world against COVID-19" and "Say no to SARS-CoV-2", which were made with the proteins structure. It might generate vaccine-related interest to broad reader categories. Finally, the evolutionary process appears to enhance the protein structure smoothly to provide suitable functionality shaped by natural selection.

Since early 2020, the entire world has been facing a disastrous outbreak of the SARS-CoV-2 virus, with massive reporting of death and infections per day. Medical practitioners adopted certain measures such as convalescent plasma therapy, antibody treatment, and injecting vaccines to eradicate the pandemic. In this review, we have primarily focused on the neutralizing antibodies presently under pre-clinical and clinical trials, focusing on their structures, binding affinity, mechanism of neutralization, and advantages over other therapeutics. We have also enlisted all the nAbs against SARS-CoV-2 and its emerging variants in different phases of clinical trials (phase-1, phase-II, and phase-III). The efficacy of administering antibody cocktails over the normal antibodies and their efficacy for the mutant variants of the SARS-CoV-2 virus in minimizing viral virulence is discussed. The potent neutralizing antibodies have eliminated many of the common problems posed by several other therapeutics. A common mechanism of the antibodies and their relevant sources have also been listed in this review.

Biomaterials are used as implants for bone and dental disabilities. However, wear particles from the implants cause osteolysis following total joint arthroplasty (TJA). Ceramic implants are considered safe and elicit a minimal response to cause periprosthetic osteolysis. However, few reports have highlighted the adverse effect of ceramic particles such as alumina (Al 2 O 3 ) on various cell types. Hence, we aimed to investigate the effect of Al 2 O 3 particles on osteoprogenitors. A comparative treatment of Al 2 O 3 , Ti, and UHMWPE particles to osteoprogenitors at a similar concentration of 200 μg/mL showed that only Al 2 O 3 particles were able to suppress the early and late differentiation markers of osteoprogenitors, including collagen synthesis, alkaline phosphatase (ALP) activity and mRNA expression of Runx2, OSX, Col1α, and OCN. Al 2 O 3 particles even induced inflammation and activated the NFkB signaling pathway in osteoprogenitors. Moreover, bone-forming signals such as the WNT/β-catenin signaling pathway were inhibited by the Al 2 O 3 particles. Al 2 O 3 particles were found to induce the mRNA expression of WNT/β-catenin signaling antagonists such as DKK2, WIF, and sFRP1 several times in osteoprogenitors. Taken together, this study highlights a mechanistic view of the effect of Al 2 O 3 particles on osteoprogenitors and suggests therapeutic targets such as NFĸB and WNT signaling pathways for ceramic particle-induced osteolysis.

The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.

COVID-19 vaccination has started throughout the globe. The vaccination program has also begun in most Asian countries. This paper analyzed the Asian-origin COVID-19 vaccines and vaccination program status in Asia till March 2021 under three sections. In the first section, we mapped the approved vaccines that originated from Asia, their technological platforms, collaborations during vaccine development, and regulatory approval from other countries. We found that a total of eight Asian COVID-19 vaccines originated and got approval from three countries: China, India, and Russia. In the second section, we critically evaluated the recent progress of COVID-19 vaccination programs. We analyzed the overall vaccination status across the Asian region. We also calculated the cumulative COVID-19 vaccine doses administered in different Asian countries, vaccine rolling in 7-day average in various Asian countries, and COVID-19 vaccine per day doses administrated in several Asian countries. We found that China and India vaccinated the maximum number of people. Finally, we evaluated the factors affecting the COVID-19 vaccination program in Asia, such as vaccine hesitancy, basic reproduction numbers (R0) and vaccination campaigns, and the cost of the vaccines. Our analysis will assist the implementation of the COVID-19 vaccination program successfully in Asia.

Biogenic silica (b-SiO 2 ) nanopowders from rice husk ash (RHA) were prepared by chemical method and their bacterial compatibility/toxicity was analyzed. The X-ray diffractometry (XRD) patterns of the b-SiO 2 nanopowders indicated an amorphous feature due to the absence of any sharp peaks. Micrographs of the b-SiO 2 revealed that sticky RHA synthesized SiO 2 nanopowder (S1) had clustered spherical nanoparticles (70 nm diameter), while b-SiO 2 nanopowder synthesized from red RHA (S2) and b-SiO 2 nanopowder synthesized from brown RHA (S3) were purely spherical (20 nm and 10 nm diameter, respectively). Compared to the S1 (11.36 m 2 g -1 ) and S2 (234.93 m 2 g -1 ) nanopowders, the S3 nanopowders showed the highest surface area (280.16 m 2 g -1 ) due to the small particle size and high porosity. The core level of the X-ray photoelectron spectroscopy (XPS) spectra showed that Si was constituted by two components, Si 2p (102.2 eV) and Si 2s (153.8 eV), while Oxygen 1s was observed at 531.8 eV, confirming the formation of SiO 2 . The anti-bacterial activity of the b-SiO 2 nanopowders was investigated using both gram-positive ( Escherichia coli ) and gram-negative ( Staphylococcus aureus ) microorganisms. Compared to S2 and S3 silica nanopowders, S1 demonstrated enhanced antibacterial activity. This study signifies the medical, biomedical, clinical, and biological importance and application of RHA-mediated synthesized b-SiO 2 .