<img src=” https://s3.amazonaws.com/production.scholastica/article/91083/large/prnano_1042023ga.jpg?1702320855”> In this era of globalization, there is a need for green synthesis of nanoparticles ...(NPs), which should lessen the tremendous energy consumption, the utilization of toxic compounds, and time, which can help save the environment from hazardous effects. Green synthesis attempts to utilize products from natural agents like plants and fungi because of their profound availability of bio compounds. The NPs derived from them exhibit anticancer, antibacterial, antimicrobial, antioxidant, anti-diabetic, and immunomodulatory properties because of their unique physical and chemical properties. These extraordinary properties make them promising agents in medicine and agriculture areas. The review has targeted the mush-room-derived NPs and bioactive compounds, including the nutritional content of mushrooms with their multipurpose properties, followed by encapsulation and delivery of the biotherapeutics. These NPs have found significant applications in advancing industrial and biomedical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and con-trol the shape and size of NPs.
Recently, yeast-derived glucan particles (GP) have emerged as novel drug delivery agents that provide for receptor-mediated uptake by phagocytic cells expressing β-glucan receptors. In our previous ...study, we prepared GP loaded with high payload (40.5
+
1.9%) of rifabutin (RB) nano-particles (RB-NPs)-GP. We investigated the anti-mycobacterial efficacy and cellular activation responses within Mycobacterium tuberculosis (M. tuberculosis) infected J774 macrophage cells following exposure to the (RB-NPs)-GP formulation. The exposure was seen to augment a robust innate immune response including the induction of reactive oxygen and nitrogen species, autophagy and apoptosis within M. tuberculosis infected macrophage. Further, the efficacy testing of these particles in murine macrophage exhibited that the (RB-NPs)-GP formulation enhanced the efficacy of RB drug by ∼2.5 fold. The study suggests that the set of innate responses conducive to killing intracellular bacteria evoked by (RB-NPs)-GP play a pivotal role in impeding the intracellular M. tuberculosis survival, resulting in enhanced efficacy of the formulation. Our results establish that the (RB-NPs)-GP formulation not only activate M. tuberculosis infected, immune-suppressed macrophage, but also adds significantly to the efficacy of loaded drug, and thus forms a promising approach that should be explored further as an alternative or adjunct form of TB therapy.
Highlights
Nano-Rifabutin loaded Glucan microparticles (RB-NPs)-GP administered to M. tuberculosis infected macrophage.
(RB-NPs)-GP induces appropriate innate immune responses in host macrophage.
Mycobactericidal Effect of Rifabutin was markedly enhanced by its nano-entrapment in GP.
Intracellular drug delivery supplements the innate response in M. tuberculosis infected macrophage.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Tuberculosis (TB) is a contagious disease that is a significant cause of illness worldwide and has been declared one of the top ten causes of mortality across the world. It is well known that ...bacteria within biofilms exhibit much higher drug resistance than individual cells. Biofilms constitute a significant threat in the clinical environment by acting as reservoirs of multidrug-resistant bacteria. Thus, the formation of biofilms has been postulated to further aid in drug insensitivity and bacterial persistence within host tissues. The rapid increase in drug resistance in Mycobacteria poses a significant challenge to TB eradication and needs to be addressed soon. In this review, we have attempted to frame a general overview of mycobacterial pathogenesis, the role of biofilm formation in enhancing its shelf life, and some natural compounds and nanoparticles as emerging novel therapeutics reported to inhibit biofilm formation in mycobacteria. Therefore, we present some recent advances which might have potential applications in new treatment regimens for Tuberculosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
<img src=” https://s3.amazonaws.com/production.scholastica/article/90699/large/prnano_1072023gaf.jpg?1701882189”> Tuberculosis is the second most fatal infectious disease; each year, it causes ...millions of deaths worldwide. Although several anti-TB drugs are currently available, the problem with these drugs is that they require a prolonged duration of treatment, with high drug doses. In addition, patient non-adherence to therapy subsequently leads to the development of multidrug-resistant and ex-tensively drug-resistant tuberculosis. Therefore, we need to develop an effective and robust nano-carrier-based drug delivery system to overcome these issues and improve the therapeutic potential of drug dose/duration and patient compliance. This review article focuses on the cur-rently available various nanotechnology-based therapeutic approaches, including lipid nanopar-ticles, polymeric particles, carbon nanotubes, glucan, and alginate-based nano-carrier systems for effective anti-TB drug delivery to host macrophage for mycobacterium killing. Finally, we also present some promising recent nanotechnology-based mycobacterial detection systems us-ing silver nanoparticles, silica nanoparticles, magnetic nanoparticles, quantum dots, and magnet-ic barcode assay that have recently emerged as the latest diagnostic tool. Functionalized nano-materials for emerging Aggregation-induced photodynamic therapy as next-generation theranostics have also been discussed as a novel option for TB diagnosis and therapy.
Mycobacterium tuberculosis (M.tb.) enoyl-acyl carrier protein (ACP) reductase (InhA) is validated as a useful target for tuberculosis therapy and is considered an attractive enzyme to drug discovery. ...This study aimed to identify the novel inhibitor of the InhA enzyme, a potential target of M.tb. involved in the type II fatty acid biosynthesis pathway that controls mycobacterial cell envelope synthesis. We compiled 80 active compounds from Ruta graveolens and citrus plants belonging to the Rutaceae family for pharmacokinetics and molecular docking analyses. The chemical structures of the 80 phytochemicals and the 3D structure of the target protein were retrieved from the PubChem database and RCSB Protein Data Bank, respectively. The evaluation of druglikeness was performed based on Lipinski’s Rule of Five, while the computed phytochemical properties and molecular descriptors were used to predict the ADMET of the compounds. Amongst these, 11 pharmacokinetically-screened compounds were further examined by performing molecular docking analysis with an InhA target using AutoDock 4.2. The docking results showed that gravacridonediol, a major glycosylated natural alkaloid from Ruta graveolens, might possess a promising inhibitory potential against InhA, with a binding energy (B.E.) of −10.80 kcal/mole and inhibition constant (Ki) of 600.24 nM. These contrast those of the known inhibitor triclosan, which has a B.E. of −6.69 kcal/mole and Ki of 12.43 µM. The binding efficiency of gravacridonediol was higher than that of the well-known inhibitor triclosan against the InhA target. The present study shows that the identified natural compound gravacridonediol possesses drug-like properties and also holds promise in inhibiting InhA, a key target enzyme of M.tb.
Microparticles containing isoniazid and rifabutin were aerosolised using a simple apparatus fabricated from a 15-ml centrifuge tube. The dose available for inhalation by rodents was determined by ...collecting microparticles emitted at the delivery port. The dose available for inhalation was proportional to durations of exposure ranging from 10 to 90
s (10.5–13.5 CV%) and the weight of powder taken for fluidization (10–50
mg,
r
2
=
0.982). The apparatus was then used to administer inhalations of microparticles to mice. Other groups of mice received free rifabutin orally, or by i.v. injection. Rifabutin was estimated in serum and tissues of dosed mice by HPLC. When ∼20
mg of microparticles were loaded in the apparatus, ∼2.5
mg were collected at the delivery port in 30
s of operation. Mice inhaled ∼300
μg of the 2.5
mg emitted at the delivery port. Airway and lung macrophages of mice receiving inhalations for 30
s accumulated 0.38
μg of rifabutin, while the amount in blood serum of these mice was 0.62
μg. In mice receiving 83
μg rifabutin i.v. or orally, the intracellular amounts were 0.06 and 0.07
μg respectively, while the amounts in serum were 1.02 and 0.80
μg. These observations confirmed that inhalation of microparticles targeted airway and lung macrophages.
Macrophage is known to readily engulf any particulate material they encounter, including invading microbes and nano- or micro-particles. While recent studies show that some microparticles (MP) are ...immunogenic even without drug-cargo, the mechanism underlying this phenomenon is yet unclear. Phagocytosis induces NADPH oxidase-2 (NOX-2) mediated ROS generation that is reported to regulate antibacterial autophagy. We therefore, investigated the role of NOX-2 derived ROS in phagosomal maturation and autophagy induction in response to phagocytic uptake of two kinds of polymeric biodegradable and biocompatible microparticles: yeast-derived β-glucan particles (YDGP) and poly-(D, L-Lactic Acid) microparticles (PMP).
J774A.1 macrophage wereas exposed to polymeric particles and the immune responses: ROS, phagosomal maturation and autophagy induction, were examined by assays including NBT, DCFH-DA, NADPH-Oxidase activity, Lysotracker and Acridine Orange. Further, the LC3 and NOX-2 expression were validated by RT-PCR, immunofluorescence assay and Western blotting. Antimicrobial activity of both MP was examined by CFU counting after administration to Mycobacterium tuberculosis and Salmonella typhimurium infected macrophage.
YDGP induces phagosomal maturation and acidic vesicle accumulation at 30 min and 24 h post-exposure, much more proficiently than that by PMP. YDGP exposure also induced NOX-2 dependent expression of light chain 3 (LC3-II), further confirmed as autophagy activation via autophagic flux assay with autophagolysosome inhibitor bafilomycin A1. Additionally, YDGP displayed superior anti-microbial activity than that by PMP.
The induction of NOX-2-dependent autophagy and antimicrobial activity exhibited by particulate glucans has significant implications in harnessing these drug delivery vehicles as potential ‘value-added’ autophagy-mediated therapeutics in future.
•YDGP induce autophagy in macrophage at 30 min and 24 h post-exposure time points.•β-Glucan induced autophagy is dependent on NOX-2 mediated ROS at both time points.•PMP activate NOX-2 and mitochondrial ROS at early and delayed time(s) respectively.•PMP do not induce autophagy at either of the time points.•YDGP administration results in decreased survival of intracellular microbes.
Japanese Encephalitis remains a significant global health concern, contributing to millions of deaths annually worldwide. Microglial cells, as key innate immune cells within the central nervous ...system (CNS), exhibit intricate cellular structures and possess molecular phenotypic plasticity, playing pivotal roles in immune responses during CNS viral infections. Particularly under viral inflammatory conditions, microglial cells orchestrate innate and adaptive immune responses to mitigate viral invasion and dampen inflammatory reactions. This review article comprehensively summarizes the pathophysiology of viral invasion into the CNS and the cellular interactions involved, elucidating the roles of various immune mediators, including pro-inflammatory cytokines, in neuroinflammation. Leveraging this knowledge, strategies for modulating inflammatory responses and attenuating hyperactivation of glial cells to mitigate viral replication within the brain are discussed. Furthermore, current chemotherapeutic and antiviral drugs are examined, elucidating their mechanisms of action against viral replication. This review aims to provide insights into therapeutic interventions for Japanese Encephalitis and related viral infections, ultimately contributing to improved outcomes for affected individuals.
Background: Circulating miRNAs (miRs) in the biofluids such as serum and plasma act as potential biomarkers
for early diagnosis, treatment and prognosis. In the present study, an attempt made to see ...the expression of miR-21
in serum of 20 cases of Oral sub-mucous fibrosis (OSMF), 20 cases of Oral squamous cell carcinoma and 40 healthy
volunteers. The expression of miR-21 was evaluated in relation to different demographical and clinicopathological
features such as sex, tobacco, pan-masala, alcohol, smoking and clinical staging respectively with an aim to identify
correlation with oral pre-cancer and cancer stages. Materials and Methods: The relative expression level of miR-21
was determined by quantitative real-time RT-PCR (qRT-PCR) in the sera of 20 OSCC, 20 OSMF patients and 40
healthy subjects as a control. Association between expression of miR-21 and OSCC clinical stages and demographical
parameters such as sex, pan-masala, tobacco, smoking, alcohol have also been analyzed in detail. Results: The results
obtained by t-test revealed significant increase in the expression level of miR-21 in OSCC as compared to OSMF. The
study also revealed the positive correlation between higher miR-21 expression and pan-masala chewers as shown by
t-test. The statistical test, ANOVA has also indicated a positive correlation between up-regulation of miR-21 in the
clinical stages of the OSCC. Conclusion: The results of present study indicated up-regulation of circulating miR-21 in
serum of OSCC as compared to OSMF (p=0.001), this study also elucidated the positive correlation between miR-21
expression in OSCC/OSMF patients, only one demographical parameter (Pan-masala) and negative correlation for
other parameters such as sex, tobacco, smoking, alcohol etc. Other findings suggested a significant increase (p=0.000)
in the expression of miR-21 in clinical staging (I-IV) of oral cancer. More studies are needed to validate it as potential
diagnostic and prognostic biomarker for OSMF and OSCC for better management.
PDF
