Causatum of Probiotic Yeast Saccharomyces cerevisiae SBO1 Supplementation on Growth and Aflatoxin Amelioration in Broilers.

Probiotics are beneficial live microorganisms that benefit the host's health when administered in the required number. They play a vital role in preventing infectious diseases caused by pathogens. The current study aimed to discover a competent probiotic microbe that can detoxify aflatoxin and promote poultry health. The yeast isolate SBO1 tolerates the temperature of 42 °C, low pH, and high bile conditions, has good auto aggregation, hydrophobicity, and exhibits improved adherence to chick intestinal epithelial cells. In addition, it has an aflatoxin detoxifying ability of 56% after 24 h. In-vivo studies in broilers resulted in a higher body weight (2138 g) and greater feed conversion efficiency in the T2 group when fed with yeast SBO1-supplemented diet. Gizzard, spleen, and bursa Fabricius were all found to weigh the same, however, a significant difference (p < 0.05) was observed in the carcass, breast yield, and fat. Therefore it was determined that adding 0.2% yeast to the broiler diet increased performance by lessening the toxin's adverse effects. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01078-5.

Advances in therapeutic applications of silver nanoparticles.

Nanotechnology is one of the most appealing area for developing new applications in biotechnology and medicine. For decades, nanoparticles have been extensively studied for a variety of biomedical applications. Silver has evolved into a potent antibacterial agent that can be used in a variety of nanostructured materials of various shapes and sizes. Silver nanoparticles (AgNP) based antimicrobial compounds are employed in a wide range of applications, including medicinal uses, surface treatment and coatings, the chemical and food industries, and agricultural productivity. When designing formulations for specific applications, the size, shape, and surface area of AgNPs are all crucial structural aspects to consider. Different methods for producing AgNPs with varying sizes and forms that are less harmful have been devised. The anticancer, anti-inflammatory, antibacterial, antiviral, and anti-angiogenic properties of AgNPs have been addressed in this review, as well as their generation and processes. Herein, we have reviewed the advances in therapeutic applications of AgNPs, as well as their limitations and barriers for future applications.

Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond.

Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NFκB), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-ß) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized.

Antimycotic effect of 3-phenyllactic acid produced by probiotic bacterial isolates against Covid-19 associated mucormycosis causing fungi.

The Covid-19 associated mucormycosis (CAM) is an emerging disease affecting immunocompromised patients. Prevention of such infections using probiotics and their metabolites persist as effective therapeutic agents. Therefore, the present study emphasizes on assessment of their efficacy and safety. Samples from different sources like human milk, honey bee intestine, toddy, and dairy milk were collected, screened and characterized for potential probiotic lactic acid bacteria (LAB) and their metabolites to be used as effective antimicrobial agents to curtail CAM. Three isolates were selected based on probiotic properties and characterized as Lactobacillus pentosus BMOBR013, Lactobacillus pentosus BMOBR061 and Pediococcus acidilactici BMOBR041 by 16S rRNA sequencing and MALDI TOF-MS. The antimicrobial activity against standard bacterial pathogens showed ˃9 mm zone of inhibition. Furthermore, the antifungal activity of three isolates was tested against Aspergillus flavus MTCC 2788, Fusarium oxysporum, Candida albicans and Candida tropicalis where the results showed significant inhibition of each fungal strain. Further studies were carried out on lethal fungal pathogens like Rhizopus sp. and two Mucor sp. which are associated with post Covid-19 infection in immunosuppressed diabetic patients. Our studies on CAM inhibitory effect of LAB revealed the efficient inhibition against Rhizopus sp. and two Mucor sp. The cell free supernatants of three LAB showed varied inhibitory activity against these fungi. Following the antimicrobial activity, the antagonistic metabolite 3-Phenyllactic acid (PLA) in culture supernatant was quantified and characterized by HPLC and LC-MS using standard PLA (Sigma Aldrich). The isolate L. pentosus BMOBR013 produced highest PLA (0.441 g/L), followed by P. acidilactici BMOBR041 (0.294 g/L) and L. pentosus BMOBR061 (0.165 g/L). The minimum inhibitory concentration of HPLC eluted PLA on the Rhizopus sp. and two Mucor sp. was found to be 180 mg/ml which was further confirmed by inhibition of total mycelia under live cell imaging microscope.

Tropolone derivative hinokitiol ameliorates cerulein-induced acute pancreatitis in mice.

Hinokitiol is a natural bio-active tropolone derivative with promising antioxidant and anti-inflammatory properties. This study was conducted to evaluate the ameliorative effects of hinokitiol against acute pancreatitis induced by cerulein. Mice were pre-treated with hinokitiol intraperitoneally for 7 days (50 and 100 mg/kg), and on the final day of study, cerulein (6 × 50 µg/kg) was injected every hour for six times. Six hours after the last dose of cerulein, blood was collected from the mice through retro-orbital plexus for biochemical analysis. After blood collection, mice were euthanized and the pancreas was harvested for studying effects on oxidative stress, pro-inflammatory cytokines, immunohistochemistry and histopathology of tissue sections. Hinokitiol treatment significantly reduced edema of the pancreas and reduced the plasma levels of lipase and amylase in mice with cerulein-induced acute pancreatitis. It also attenuated the oxidative and nitrosative stress related damage as evident from the reduced malondialdehyde (MDA) and nitrite levels, which were significantly increased in the mice with acute pancreatitis. Furthermore, hinokitiol administration significantly reduced the pancreatitis-evoked decrease in the activity of catalase, glutathione (GSH) and superoxide dismutase (SOD) in the pancreatic tissue. Pre-treatment with hinokitiol significantly reduced the elevated levels of pro-inflammatory cytokines like interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α) as well as increased the levels of anti-inflammatory cytokine interleukin-10 (IL-10) in the pancreatic tissue of mice with acute pancreatitis. The immunohistochemical expression of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), cyclooxygenase (COX-2) and TNF-α were significantly decreased by hinokitiol in mice with cerulein-induced acute pancreatitis. In conclusion, the results of the present study demonstrate that hinokitiol has significant potential to prevent cerulein-induced acute pancreatitis.

Gene therapy: Comprehensive overview and therapeutic applications.

Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short tandem repeats (CRISPR)/CRISPR-associated protein (Cas)-associated nucleases. Transfer of gene is either through transformation where under specific conditions the gene is directly taken up by the bacterial cells, transduction where a bacteriophage is used to transfer the genetic material and lastly transfection that involves forceful delivery of gene using either viral or non-viral vectors. The non-viral transfection methods are subdivided into physical, chemical and biological. The physical methods include electroporation, biolistic, microinjection, laser, elevated temperature, ultrasound and hydrodynamic gene transfer. The chemical methods utilize calcium- phosphate, DAE-dextran, liposomes and nanoparticles for transfection. The biological methods are increasingly using viruses for gene transfer, these viruses could either integrate within the genome of the host cell conferring a stable gene expression, whereas few other non-integrating viruses are episomal and their expression is diluted proportional to the cell division. So far, gene therapy has been wielded in a plethora of diseases. However, coherent and innocuous delivery of genes is among the major hurdles in the use of this promising therapy. Hence this review aims to highlight the current options available for gene transfer along with the advantages and limitations of every method.

Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis.

Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis.

Critical neurological features of COVID-19: Role of imaging methods and biosensors for effective diagnosis.

COVID-19 is a respiratory infection that has been declared as a global health crisis by the WHO. It mainly affects the respiratory system. Apart from respiratory system, it also affects other organs as well including the brain. Numerous emerging reports have demonstrated that the COVID-19 has detrimental effects on neurological functions, and can lead to severe impairment of the central nervous system (CNS). The neurological manifestations linked with COVID-19 include headache, anosmia, encephalitis, epileptic seizures, Guillain-Barre syndrome, stroke and intracerebral hemorrhage alongwith multiple others complications. The CNS related complications may be severe and are linked with poor diagnosis which may worsen the condition. Therefore, there is a need to precisely understand the neurological sequelae along with upcoming clinical outcomes. Here, we present a brief review of the neurological complications and symptoms associated with COVID-19 along with brain imaging findings. Further, we have discussed about the emerging biosensing approaches which may aid in rapid, precise and mass diagnosis of COVID-19.

Silver nanoparticle based multifunctional approach for combating COVID-19.

COVID-19 is a highly contagious and widespread disease that has strained the global healthcare system to the hilt. Silver nanoparticles (AgNPs) are well known for their potent antimicrobial, antiviral, immunomodulatory and biosensing properties. AgNPs have been found to be potential antiviral agent that act against many deadly viruses and is presumed to be effective against COVID-19. AgNPs can generate free radicals and reactive oxygen species (ROS) leading to apoptosis mediated cell death thereby inhibiting viral infection. The shape and size of AgNPs play an important role in its biomedical applications as alterations may result in variable biological interaction and activity. Herein, we propose that AgNPs can be utilized for effective management of the ongoing COVID-19 pandemic by highlighting the current status of AgNPs in the fight against COVID-19.

Preclinical efficacy study of a porous biopolymeric scaffold based on gelatin-hyaluronic acid-chondroitin sulfate in a porcine burn injury model: role of critical molecular markers (VEGFA, N-cadherin, COX-2), gamma sterilization efficacy and a comparison of healing potential to Integra™.

Development of scaffold from biopolymers can ease the requirements for donor skin autograft and plays an effective role in the treatment of burn wounds. In the current study, a porous foam based, bilayered hydrogel scaffold was developed using gelatin, hyaluronic acid and chondroitin sulfate (G-HA-CS). The fabricated scaffold was characterized physicochemically for pre- and post-sterilization efficacy by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA).In-vitrostudies proved that the scaffold promoted cellular proliferation. The efficacy of G-HA-CS scaffold was compared with Integra™ at different time points (7, 14, 21 and 42 days), in a swine second degree burn wound model. Remarkable healing potential of the scaffold was evident from the wound contraction rate, reduction of IL-6, TNF-αand C3. The expression of healing markers TGF-ß1 and collagen 1 revealed significant skin regeneration with regulated fibroblast activation towards the late phase of healing (p< 0.001 at day 21 and 42 vs. control). Expression of Vascular Endothelial Growth Factor A (VEGFA), vimentin and N-cadherin were found to favor angiogenesis and skin regeneration. Mechanistically, scaffold promoted wound healing by modulation of CD-45, cyclooxygenase-2 and MMP-2. Thus, the promising results with foam based scaffold, comparable to Integra™ in swine burn injury model offer an innovative lead for clinical translation for effective management of burn wound.

Decorin as a possible strategy for the amelioration of COVID-19.

Coronavirus pandemic has emerged as an extraordinary healthcare crisis in modern times. The SARS-CoV-2 novel coronavirus has high transmission rate, is more aggressive and virulent in comparison to previously known coronaviruses. It primarily attacks the respiratory system by inducing cytokine storm that causes systemic inflammation and pulmonary fibrosis. Decorin is a pluripotent molecule belonging to a leucine rich proteoglycan group that exerts critical role in extracellular matrix (ECM) assembly and regulates cell growth, adhesion, proliferation, inflammation, and fibrogenesis. Interestingly, decorin has potent anti-inflammatory, cytokine inhibitory, and anti-fibrillogenesis effects which make it a potential drug candidate against the COVID-19 related complications especially in the context of lung fibrosis. Herein, we postulate that owing to its distinctive pharmacological actions and immunomodulatory effect, decorin can be a promising preclinical therapeutic agent for the therapy of COVID-19.

Role of nanotechnology behind the success of mRNA vaccines for COVID-19.

The emergency use authorization (EUA) by the US-FDA for two mRNA-based vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) has brought hope of addressing the COVID-19 pandemic which has killed more than two million people globally. Nanotechnology has played a significant role in the success of these vaccines. Nanoparticles (NPs) aid in improving stability by protecting the encapsulated mRNA from ribonucleases and facilitate delivery of intact mRNA to the target site. The overwhelming success of these two mRNA based vaccines with ~95% efficacy in phase III clinical trials can be attributed to their unique nanocarrier, the "lipid nanoparticles" (LNPs). LNPs are unique compared with bilayered liposomes and provide improved stability of the cargo, possess rigid morphology, and aid in better cellular penetration. This EUA is a major milestone and showcases the immense potential of nanotechnology for vaccine delivery and for fighting against future pandemics. Currently, these two vaccines are aiding in the alleviation of the COVID-19 health crisis and demonstrate the potential utility of nanomedicine for tackling health problems at the global level.

Can bilirubin nanomedicine become a hope for the management of COVID-19?

Bilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications.

Emerging Role of PD-1/PD-L1 Inhibitors in Chronic Liver Diseases.

Programmed cell death protein 1 (PD-1)/PD-ligand (L)1, the immune checkpoint inhibitors have emerged as a promising strategy for the treatment of various diseases including chronic liver diseases (CLDs) such as hepatitis, liver injury and hepatocellular carcinoma (HCC). The role of PD-1/PD-L1 has been widely inspected in the treatment of viral hepatitis and HCC. PD-1 is known to play a crucial role in inhibiting immunological responses and stimulates self-tolerance by regulating the T-cell activity. Further, it promotes apoptosis of antigen-specific T-cells while preventing apoptosis of Treg cells. PD-L1 is a trans-membrane protein which is recognized as a co-inhibitory factor of immunological responses. Both, PD-1 and PD-L1 function together to downregulate the proliferation of PD-1 positive cells, suppress the expression of cytokines and stimulate apoptosis. Owing to the importance of PD-1/PD-L1 signaling, this review aims to summarize the potential of PD-1/PD-L1 inhibitors in CLDs along with toxicities associated with them. We have enlisted some of the important roles of PD-1/PD-L1 in CLDs, the clinically approved products and the pipelines of drugs under clinical evaluation.

Potential of electric stimulation for the management of COVID-19.

The COVID-19 pandemic is the most devastating health emergency that humans have seen over the past century. The war against the disease has been handicapped by unavailability of effective therapeutic options. Till date, there is no clinically approved vaccine or drug for the treatment of COVID-19, and the ongoing search to find a novel therapy is progressing at pandemic pace. Herein, we propose a novel hypothesis based on sound research evidence that electric stimulation can be a potential adjuvant to the currently used symptomatic therapies and antiviral drugs. Based on preclinical evidence, we propose that electric stimulation can improve respiratory functions, inhibit SARS-CoV-2 growth, reduce pain, boost immunity and improve the penetration of antiviral drugs. We envisage that our hypothesis, if used clinically as an adjuvant, may significantly improve the therapeutic outcomes of the current treatment regimen being used around the globe for the management of COVID-19.