Green synthesis of silver nanoparticles employing hamdard joshanda extract: putative antimicrobial potential against gram positive and gram negative bacteria.

The bio-mediated synthesis of nanoparticles offers a sustainable and eco-friendly approach. In the present study, silver nanoparticles (AgNPs) were synthesized using Joshanda extract, a commercially available herbal formulation derived from a traditional medicinal plant, as a reducing and stabilizing agent. The as-synthesized AgNPs were characterized using UV-Vis spectroscopy, dynamic light scattering (DLS), X-ray Diffraction (XRD) study, and Fourier-transform infrared (FTIR) analysis. UV-Vis spectroscopy exhibited a prominent absorption peak at 430 nm, confirming the formation of AgNPs. DLS analysis revealed the size distribution of the nanoparticles, ranging from 80 to 100 nm, and zeta potential measurements indicated a surface charge of - 14.4 mV. The XRD analysis provide evidence for the presence of a face-centered cubic structure within the silver nanoparticles. FTIR analysis further elucidated the interaction of bioactive compounds from the Joshanda extract with the AgNPs' surface. Strong peaks at 765-829 cm-1 indicated C-Cl stretching vibrations of alkyl halides, while the stretching of alkenes C=C was observed at 1641 cm-1. Moreover, the presence of alcohols and phenol (OH) groups was identified at 3448 cm-1, suggesting their involvement in nanoparticle stabilization. The antimicrobial potential of the synthesized AgNPs was evaluated against both gram-negative Pseudomonas aeruginosa and gram-positive Streptococcus mutans using zone of inhibition assays. The AgNPs exhibited remarkable inhibitory effects against both types of bacteria. Additionally, AgNPs-treated groups demonstrated a significant increase in reactive oxygen species (ROS) levels, indicating potential of as-synthesized AgNPs in disruption of the target microbial membranes. Furthermore, the as-synthesized AgNPs exhibited notable anti-biofilm properties by effectively hindering the development of mature biofilms. This study highlights the efficient green synthesis of AgNPs using Joshanda extract and also provides insights into their physico-chemical properties of as-synthesized nanoparticles. The demonstrated antimicrobial activity against both gram-negative and gram-positive bacteria, along with biofilm inhibition potential, underscores the promising applications of the as-synthesized AgNPs in the field of biomedical and environmental sciences. The study bridges traditional knowledge with contemporary nanotechnology, offering a novel avenue for the development of eco-friendly antimicrobial agents.

Potential of siRNA-Bearing Subtilosomes in the Treatment of Diethylnitrosamine-Induced Hepatocellular Carcinoma.

Therapeutics, based on small interfering RNA (siRNA), have demonstrated tremendous potential for treating cancer. However, issues such as non-specific targeting, premature degradation, and the intrinsic toxicity of the siRNA, have to be solved before they are ready for use in translational medicines. To address these challenges, nanotechnology-based tools might help to shield siRNA and ensure its specific delivery to the target site. Besides playing a crucial role in prostaglandin synthesis, the cyclo-oxygenase-2 (COX-2) enzyme has been reported to mediate carcinogenesis in various types of cancer, including hepatocellular carcinoma (HCC). We encapsulated COX-2-specific siRNA in Bacillus subtilis membrane lipid-based liposomes (subtilosomes) and evaluated their potential in the treatment of diethylnitrosamine (DEN)-induced hepatocellular carcinoma. Our findings suggested that the subtilosome-based formulation was stable, releasing COX-2 siRNA in a sustained manner, and has the potential to abruptly release encapsulated material at acidic pH. The fusogenic property of subtilosomes was revealed by FRET, fluorescence dequenching, content-mixing assay, etc. The subtilosome-based siRNA formulation was successful in inhibiting TNF-α expression in the experimental animals. The apoptosis study indicated that the subtilosomized siRNA inhibits DEN-induced carcinogenesis more effectively than free siRNA. The as-developed formulation also suppressed COX-2 expression, which in turn up-regulated the expression of wild-type p53 and Bax on one hand and down-regulated Bcl-2 expression on the other. The survival data established the increased efficacy of subtilosome-encapsulated COX-2 siRNA against hepatocellular carcinoma.

Amphotericin B Nano-Assemblies Circumvent Intrinsic Toxicity and Ensure Superior Protection in Experimental Visceral Leishmaniasis with Feeble Toxic Manifestation.

In spite of its high effectiveness in the treatment of both leishmaniasis as well as a range of fungal infections, the free form of the polyene antibiotic amphotericin B (AmB) does not entertain the status of the most preferred drug of choice in clinical settings. The high intrinsic toxicity of the principal drug could be considered the main impedance in the frequent medicinal use of this otherwise very effective antimicrobial agent. Taking into consideration this fact, the pharma industry has introduced many novel dosage forms of AmB to alleviate its toxicity issues. However, the limited production, high cost, requirement for a strict cold chain, and need for parenteral administration are some of the limitations that explicitly compel professionals to look for the development of an alternate dosage form of this important drug. Considering the fact that the nano-size dimensions of drug formulation play an important role in increasing the efficacy of the core drug, we employed a green method for the development of nano-assemblies of AmB (AmB-NA). The as-synthesized AmB-NA manifests desirable pharmacokinetics in the treated animals. The possible mechanistic insight suggested that as-synthesized AmB-NA induces necrosis-mediated cell death and severe mitochondrial dysfunction in L. donovani promastigotes by triggering depolarization of mitochondrial membrane potential. In vivo studies demonstrate a noticeable decline in parasite burden in the spleen, liver, and bone marrow of the experimental BALB/c mice host. In addition to successfully suppressing the Leishmania donovani, the as-formed AmB-NA formulation also modulates the host immune system with predominant Th1 polarization, a key immune defender that facilitates the killing of the intracellular parasite.

Patho-Physiology of Aging and Immune-Senescence: Possible Correlates With Comorbidity and Mortality in Middle-Aged and Old COVID-19 Patients.

During the last 2 years, the entire world has been severely devastated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) as it resulted in several million deaths across the globe. While the virus infects people indiscriminately, the casualty risk is higher mainly in old, and middle-aged COVID-19 patients. The incidences of COVID-19 associated co-morbidity and mortality have a great deal of correlation with the weakened and malfunctioning immune systems of elderly people. Presumably, due to the physiological changes associated with aging and because of possible comorbidities such as diabetes, hypertension, obesity, cardiovascular, and lung diseases, which are more common in elderly people, may be considered as the reason making the elderly vulnerable to the infection on one hand, and COVID-19 associated complications on the other. The accretion of senescent immune cells not only contributes to the deterioration of host defense, but also results in elevated inflammatory phenotype persuaded immune dysfunction. In the present review, we envisage to correlate functioning of the immune defense of older COVID-19 patients with secondary/super infection, increased susceptibility or aggravation against already existing cancer, infectious, autoimmune, and other chronic inflammatory diseases. Moreover, we have discussed how age-linked modulations in the immune system affect therapeutic response against administered drugs as well as immunological response to various prophylactic measures including vaccination in the elderly host. The present review also provides an insight into the intricate pathophysiology of the aging and the overall immune response of the host to SARS-CoV-2 infection. A better understanding of age-related immune dysfunction is likely to help us in the development of targeted preemptive strategies for deadly COVID-19 in elderly patients.