Current Research in Biotechnology最新文献

Many microorganisms pose a threat to human health due to the ever-increasing bacterial resistance to conventional drugs. Nowadays, searching for new alternatives to conventional antibiotics to fight bacterial resistance is a main task. Thus, natural molecules such as amino acids and peptides arise as possible solutions to the problem. The antimicrobial activity of targeted compounds was studied by the agar-diffusion method, using the prepared working solutions of the targeted peptides with the corresponding concentrations. The results of the antimicrobial activity against different test pathogens show specificity, as antimicrobial activity against the used test microorganisms was not found in the investigated short-chain synthetic peptides Si6, Si3 and Si13. Antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Staphylococcus epidermidis, Propionibacterium acnes, Escherichia coli, Pseudomonas aeruginosa, and the yeasts Malassezia furfur and Candida albicans was established for the long-chain synthetic peptides Si1, Si5 and Si16, except Si5 which does not show activity against pathogenic fungal strain C. albicans. The compound Si16 where natural Leu in (KLAKLAK)₂-NH₂ is replaced by unnatural Nle is the best candidate for medical drug due to the combined antibacterial and antiproliferative effect as well as long hydrolytic stability.

Biodiesel production from microalgae is considered one of the main candidates to replace conventional fuels. In addition, the use of ultrasound can be crucial to enhance different steps in the industrial production of this biofuel from this type of microorganisms. This review focuses on the potential of ultrasound technology to increase lipid content in microalgae and improve biomass harvesting and lipid extraction, as well as its potential use in oil transesterification. Specifically, the use of ultrasound pulses in the stationary phase of microalgae growth can act as a stimulus to improve lipid content and can oxidise cell walls, improving lipid extraction and subsequent harvesting. Furthermore, if assisted with ultrasound, the reaction time, alcohol/oil molar ratio, separation process, and energy consumption of transesterification can be reduced compared to conventional methods due to the reduction of the interfacial area. Finally, ultrasound technology can be used if some of the previous processes (i.e., in situ transesterification) are coupled to decrease the number of steps in an industrial process. Regarding scale-up, although some ultrasonic reactors working in continuous operation mode have already been proposed, there are still some drawbacks, mainly related to the knowledge of bubble behaviour in different media and their effect on reactions (enzymatic or in situ transesterifications) as well as the energy consumption if ultrasound technology is used in more than one process simultaneously. These facts need to be studied in more detail to introduce this technology in a large-scale process.

RNA therapeutics are promising for the treatment of lung diseases where small molecules and biologics have failed to have much success in the past. While siRNA and mRNA drugs are now FDA-approved for rare diseases in the liver and as vaccines for infectious diseases, they became clinically established only after suitable advances in drug delivery platforms, such as the case of lipid nanoparticles. Localized delivery of RNA therapeutics through nanocarriers optimized for inhaled administration has the potential to address respiratory diseases without toxicity concerns from off-target effects. Here, we review recent clinical and preclinical progress of nanocarriers for inhaled RNA delivery, analyze the properties of nanocarrier-mediated FDA-approved drugs for respiratory diseases, and highlight compelling efficacy endpoints anticipated from ongoing clinical programs. We also present an overview of physiological challenges and opportunities that impact delivery of inhaled RNA therapeutics to the lungs. Finally, we discuss relevant models for preclinical testing, and translational considerations that can be used to help develop future nanocarriers for inhaled administration of RNA therapeutics.

Citrus viral infections pose a substantial threat to the global citrus industry, resulting in multitudinous economic losses annually. Timely and precise identification of citrus viruses offers a promising avenue for proactive insights preemptively before the instigation of extensive infections. The present study was devised to expedite the prompt identification of the presence of Citrus tristeza virus (CTV) within Nepalese citrus species utilizing a Double Antibody Sandwich-Enzyme-Linked Immunosorbent Assay (DAS-ELISA), followed by its validation using reverse transcription PCR (RT-PCR). Samplings extracted from plants harvested from 74 out of the 77 administrative districts within Nepal provide substantial evidence of extensive propagation of viral contagion among citrus cultivars across 64 districts (86.48%) of the nation. A comprehensive analysis of the samples obtained from diverse geographical localities revealed that 36 districts (48.64%) exhibit mild infestation, while 9 districts (12.16%) evince moderate infestation. Moreover, samples harvested from 19 districts (25.67%) were highly infected; intriguingly, specimens from 10 districts (13.51%) manifest an absence of viral intrusion. The results have been validated with RT-PCR assay. Given the profound significance of citrus as a pivotal repository of vitamin C and its essential role in conferring advantageous health attributes to humankind, alongside its substantial contribution to the economic paradigm, a meticulous examination is imperative to safeguard these plants against an array of viral infections. Collectively, the DAS-ELISA methodology along with RT-PCR approaches constitutes an exquisitely sensitive and meticulously specific modality, poised to accelerate the expeditious detection of citrus-associated viruses within burgeoning economies like Nepal. This advancement supports timely and precise detection and diagnosis of agriculturally virulent conditions, thereby forestalling the eruption of viral epidemics and concomitantly curbing their financial repercussions.

7-ketocholesterol is a cytotoxic oxysterol which is frequently increased in many chronic inflammatory and age-related diseases. Thus, the inhibition of the toxicity of 7-ketocholesterol is a major challenge to treat these diseases. 158N oligodendrocytes were used to evaluate the cytoprotective effects of lipids: ω-3 and ω-9 fatty acids (α-linolenic acid (C18:3n-3), eicosapentaenoic acid (C20:5n-3), docosahexaenoic acid (C22:6n-3), erucic acid (C22:1n-9) and oleic acid (C18:1n-9)), Lorenzo's oil (a mixture of oleic and erucic acid, 4:1) and sulfo-N-succinimidyl oleate (SSO, a synthetic derivative of oleic acid). On 158N cells, the ability of these molecules to inhibit 7KC-induced oxiapoptophagy (plasma membrane alteration, loss of ΔΨm, peroxisomal dysfunction, reactive oxygen species overproduction, induction of apoptosis and autophagy) were determined. ARPE-19 epithelial retinal cells were also used to evaluate the cytoprotective effect of SSO on 7KC-induced cell death. Unlike ω-3 and ω-9 fatty acids and Lorenzo's oil, sulfo-N-succinimidyl oleate had no cytotoxic effects over a wide range of concentrations. Noteworthy, unlike fatty acids and Lorenzo's oil, the cytoprotective effects of sulfo-N-succinimidyl oleate on 7KC-induced oxiapoptophagy, a caspase-dependent mode of cell death on 158N cells, were not associated with an accumulation of lipid droplets. In addition, on ARPE-19 cells, sulfo-N-succinimidyl oleate prevented 7KC-induced oxidative stress and cell death. These different characteristics of SSO make it possible to envisage its use for therapeutic purposes in diseases where 7-ketocholesterol levels are increased without eventual secondary side effects due to lipid droplets formation.

Nanozymes are a class of nanoparticles that can mimic enzyme activity and be used for various applications in modern clinical therapy. It has recently been observed that nanozymes have multi-enzyme mimicking activities, are highly stable, versatile and easily modified. Moreover, they have high catalytic efficiency, high recovery rates, improved substrate specificity and are suitable for mass production. The catalytic mechanisms of nanozymes mainly include catalase, peroxidase, oxidase, hydrolase and superoxide dismutase-like activities, which enable nanozymes to be used as potential therapeutics against a plethora of infectious and lifestyle disorders. Nanozymes have been used as therapeutics against cancer, inflammatory diseases, neurodegenerative and neurological disorders, bacterial, fungal and viral infections, wounds and diseases associated with Reactive Oxygen Species. The purpose of writing this review is to provide a comprehensive compilation of novel research work that has taken place in the last few years regarding the use of nanozymes for therapy. We have compiled the various kinds of nanozymes and elaborated on their anti-tumorigenic, antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, and neuroprotective roles. Their modes of action and enzymatic targets have also been discussed. The types and mechanisms of synthesis of nanozymes have also been summarized, along with interactions of nanoparticles with nanozymes. Furthermore, strategies to enhance the compatibility between nanoparticles and nanozymes have also been analyzed. Major focus has been laid on therapeutic applications of nanozymes. The challenges and future perspectives of using nanozymes in clinical therapy have also been debated in the later sections.

Diabesity is the concurrence of both diabetes and obesity, and it has become a modern epidemic. It is linked by numerous common pathophysiological mechanisms which can be targeted to combat its harms. The available treatments for diabesity include the medications that are also causing several adverse side effects. The increasing healthcare costs, both direct and indirect, for diabesity management continue to rise, underscoring the urgency to find efficient and cost-effective treatment methods. These circumstances have prompted a shift in research towards exploring natural dietary alternatives for treatment. Among these dietary substitutes, citrus fruits rich in polyphenols have caught the attention of researchers. This review narrates the major interconnection of diabesity and brings out the various mechanisms in which citrus polyphenols can be used for its management. Citrus polyphenols fight against diabesity by targeting adipokines, reactive oxygen species, leptin deficiency, metabolic endotoxemia, peroxisomes proliferator activating receptors, insulin signaling, starch hydrolyzing enzymes, and human islet amyloid polypeptide. The studies on the role of citrus polyphenols in the treatment of diabesity have shown clearly that addressing various physiological systems which can interact with citrus polyphenols can help to manage diabesity and related health concerns.

Nitrous oxide (N₂O) emissions from the wastewater treatment sector are a significant contributor to global greenhouse gas levels. This investigation delves into the mechanisms of N₂O generation and uptake, correlating microbial processes with variables such as influent characteristics and operational parameters. The nature of carbon substrates in the influent profoundly influences microbial consortia and N₂O output. Elevating the carbon-to-nitrogen (C/N) ratio has been shown to curtail N₂O emissions by alleviating the competitive dynamics among denitrifying enzymes. Optimal activity of N₂O reductase is achieved by maintaining a neutral to mildly alkaline pH and stable ambient temperatures. It is imperative to circumvent extreme aeration rates and prolonged aeration periods to reduce N₂O release. The study underscores the importance of an effective carbon feed strategy and advocates for prolonged hydraulic retention times (HRT) and sludge retention times (SRT) in activated sludge suspension systems to inhibit N₂O escape. Notably, excessive internal recycling, coupled with heightened dissolved oxygen (DO) levels in aerobic zones, intensifies N₂O emission risks. Moreover, the presence of hazardous contaminants, such as heavy metals and antibiotics, interferes with nitrogen elimination processes, warranting a comprehensive assessment of consequent N₂O emission hazards. This research provides a scientific basis as well as practical management approaches to diminish N₂O emissions.

Coronavirus disease 2019 (COVID-19) still remains the most disastrous infection continuously affecting millions of people worldwide. Herein, we performed a comparative study between the anti-influenza drug favipiravir (FAV) and the anti-thalassemia drug deferiprone (DFP) in order to examine their potential as basic scaffolds for the generation of most effective and structurally novel antivirals. To conduct the initial molecular modelling and virtual screening steps, our recently proposed single crystal X-ray diffraction (SCXRD)/HYdrogen DEssolvation (HYDE) technology platform has been used. This platform allows molecular design, interactive prioritization and virtual evaluation of newly designed molecules, simultaneously affecting two COVID-related targets, including angiotensin-converting enzyme 2 (ACE2) as a host-cellular receptor (host-based approach) and the main protease (M^pro) enzyme of the spike glycoprotein of SARS-Cov-2 (virus-based approach). Based on the molecular docking results, DFP has shown higher binding affinity (K_{i HYDE} values) over FAV towards both biological targets. The tautomeric, physicochemical, and biological properties of FAV and DFP have been studied both experimentally and theoretically using molecular spectroscopy (UV–VIS absorption), parallel artificial membrane permeability assay, and cell biology (PAMPA and MTT assay), as well as DFT quantum chemical calculations. According to the obtained results, the enol tautomers of both compounds are considerably more stable in different organic solvents. However, the keto tautomer of FAV was estimated to be most preferable under physiological conditions, which is in good agreement with the molecular docking studies. The isolated crystal structure of DFP is in an excellent agreement with the computation in respect of the most stable tautomer. Combined single X-ray/molecular modeling studies including HYDE analyses provided not only insights into the protein–ligand interactions within the binding site of SARS-Cov-2-ACE2 and SARS-Cov-2-M^pro, but also a valuable information regarding the most stable enol tautomeric form of DFP that contributes to its estimated higher potency against these targets.

To delineate the response mechanism of Nile tilapia (Oreochromis niloticus) to the riverine pollution of river Ganga, a comparative transcriptomic analysis was performed utilizing fresh liver through RNA-Seq technology. A total of 51.39 million and 32.8 million reads were obtained after excluding low quality sequences from non-polluted (Barrackpore) and polluted (Kanpur) sites of Nile tilapia. About 81.4 % and 95.3% reads were perfectly mapped with the reference sequence of O. niloticus. Transcriptional analysis generated 363 differential expressed genes (DEGs) including 131 up-regulated and 232 down-regulated genes. Gene Ontology (GO) enrichment analysis revealed that significant DEGs were associated with ribosome biogenesis, alpha-amino acid metabolic process, translational initiation etc. as biological process (BP); unfolded protein binding, vitamin binding, carboxylic acid binding and etc. as molecular function (MF); ribosome, and ribosomal subunit as cellular component (CC). The KEGG analysis indicated that these DEGs were highly involved in ribosome, Lysine degradation and RNA transport pathways. Additionally, ten hub genes participated in Translation, Ribonucleoprotein complex biogenesis as BP, Ribosome, Eukaryotic translation initiation factor 3 complex as CC and Structural constituent of ribosome, RNA binding as MF were affected in riverine pollution. Overall, this transcriptome investigation provided an extensive overview of pollution triggered transcriptional mechanisms in Tilapia liver and would be highly significant for further exploration of the molecular processes in response to pollution.