Biolmpacts
Volume:14 Issue: 6, Nov 2024

In this perspective review, we evaluated the clinical management of fatal fentanyl overdose in several routes of administration, concentrating on both legally prescribed and illegally produced formulations.

A literature search was conducted on Web of Science, PubMed, and Google Scholar databases, using the following keywords: fentanyl, illicit fentanyl, deaths, misuse, abuse, and naloxone. We included only articles whose abstracts were available in English. All articles were screened using their abstracts to determine their relevance to the current review.

The gold standard for treating both acute and chronic pain is fentanyl, but abuse of the drug has exploded globally since the late 2000s. Fentanyl abuse has been shown to frequently result in serious harm and even death.

By educating patients and physicians, making rescue kits easily accessible, developing vaccines to prevent opioid addiction, and perhaps even creating new tamper-resistant fentanyl formulations, it may be possible to prevent fentanyl misuse, therapeutic errors, and the repercussions that follow.

Alpha-lipoic acid (ALA) has garnered significant attention for its potential therapeutic benefits across a wide spectrum of health conditions. Despite its remarkable antioxidant properties, ALA is hindered by challenges such as low bioavailability, short half-life, and unpleasant odor. To overcome these limitations and enhance ALA's therapeutic efficacy, various nanoparticulate drug delivery systems have been explored. This comprehensive review evaluates the application of different nanoparticulate carriers, including lipid-based nanoparticles (solid lipid nanoparticles, niosomes, liposomes, nanostructured lipid carriers (NLCs), and micelles), nanoemulsions, polymeric nanoparticles (nanocapsules, PEGylated nanoparticles, and polycaprolactone nanoparticles), films, nanofibers, and gold nanoparticles, for ALA delivery. Each nanoparticulate system offers unique advantages, such as improved stability, sustained release, enhanced bioavailability, and targeted delivery. For example, ALA-loaded SLNs demonstrated benefits for skin care products and skin rejuvenation. ALA encapsulated in niosomes showed potential for treating cerebral ischemia, a condition largely linked to stroke. ALA-loaded cationic nanoemulsions showed promise for ophthalmic applications, reducing vascular injuries, and corneal disorders. Coating liposomes with chitosan further enhanced stability and performance, promoting drug absorption through the skin. This review provides a comprehensive overview of the advancements in nanoparticulate delivery systems for ALA, highlighting their potential to overcome the limitations of ALA administration and significantly enhance its therapeutic effectiveness. These innovative approaches hold promise for the development of improved ALA-based treatments across a broad spectrum of health conditions.

The discovery of gene editing techniques has opened a new era within the field of biology and enabled scientists to manipulate nucleic acid molecules. CRISPR-Cas9 genome engineering has revolutionized this achievement by successful targeting the DNA molecule and editing its sequence. Since genomic changes are the basis of the birth and growth of many tumors, CRISPR-Cas9 method has been successfully applied to identify and manipulate the genes which are involved in initiating and driving some neoplastic processes.

By review of the existing literature on application of CRISPR-Cas9 in cancer, different databases, such as PubMed and Google Scholar, we started data collection for "CRISPR-Cas9", "Genome Editing", "Cancer", "Solid tumors", "Hematologic malignancy" "Immunotherapy", "Diagnosis", "Drug resistance" phrases. Clinicaltrials.gov, a resource that provides access to information on clinical trials, was also searched in this review.

We have defined the basics of this technology and then mentioned some clinical and preclinical studies using this technology in the treatment of a variety of solid tumors as well as hematologic neoplasms. Finally, we described the progress made by this technology in boosting immune-mediated cell therapy in oncology, such as CAR-T cells, CAR-NK cells, and CAR-M cells.

CRISPR-Cas9 system revolutionized the therapeutic strategies in some solid malignant tumors and leukemia through targeting the key genes involved in the pathogenesis of these cancers.

COVID-19 is an RNA virus belonging to the SARS family of viruses and includes a wide range of symptoms along with effects on other body organs in addition to the respiratory system. The high speed of transmission, severe complications, and high death rate caused scientists to focus on this disease. Today, many different investigation types are performed on COVID-19 from various points of view in the literature. This review summarizes most of them to provide a useful guideline for researchers in this field. After a general introduction, this review is divided into three parts. In the first one, various transmission ways COVID-19 are classified and explained in detail. The second part reviews the used biological samples for the detection of virus and the final section describes the various methods reported for the diagnosis of COVID-19 in various biological matrices.

Peptides from lactic acid bacteria provide health benefits and can inhibit the growth of pathogenic organisms. The present work aimed to isolate and characterize peptides with antibacterial activity from Lactobacillus plantarum 1407.

Peptides were isolated and purified from L. plantarum 1407. The effect of various physiological parameters on the antibacterial activity of the isolated peptides was analyzed. The mode of action of the peptides on indicator organisms was observed using transmission microscopy analysis and flow cytometry analysis .

Antibacterial activity and mode of action of peptides isolated from L. plantarum 1407 against gram-positive and gram-negative bacteria have been studied. L. plantarum culture exhibited maximum antibacterial activity at 40 °C, pH 8, and 0.7% salt concentration. The cell-free supernatant (CFS) was concentrated using a 3 kDa ultrafiltration membrane and the peptide fractions (<3 kDa) were further fractionated using Sephadex G-25 gel filtration chromatography. The antibacterial activity of the eluted fractions (F1 to F4) was evaluated using flow cytometry and transmission electron microscopy. F3 fraction exhibited increased antibacterial activity than F1, F2, and F4 fractions against the indicator organisms. Cell membrane damage and leakage of cytoplasmic content of the bacterial cells treated with the antibacterial F3 fraction peptides were observed.

The active peptides from L. plantarum 1407 can be potentially used for the treatment of bacterial infections.

To explore the correlation between the tumour mutation burden (TMB) and prognosis and its clinical significance among patients with stage III gastric cancer (GC).

Patients with stage III GC were divided into a high TMB and low TMB group in both a study cohort of 38 patients and the Cancer Genome Atlas (TCGA) cohort of 173 patients. In the study cohort, next-generation sequencing was used to detect mutated GC genes and obtain TMB data. In the TCGA cohort, gene set enrichment analysis was performed, and the relationship between TMB, prognosis and clinicopathologic factors was analysed. Western blot and quantitative real-time polymerase chain reaction were used to detect the expression levels of both proteins and genes. Cell viability was measured using methyl thiazolyl tetrazolium and transwell cell assays.

Patients in the high TMB group had better overall survival (OS) rates than patients in the low TMB group for both cohorts and TMB was associated with age, mutation signature 1 and mutation signature 17. The Cox regression analysis revealed that age, not TMB, was an independent prognosis factor. Furthermore, genes with high-frequency mutations were significantly enriched in the Notch and RTK-RAS signalling pathways. The activation of these pathways was lower in the high TMB compared with the low TMB group, and the proliferation and migration abilities of GC cells showed a similar pattern in both TMB groups.

Patients in the high TMB group had better OS rates than patients in the low TMB group. Genes with high-frequency mutations were significantly enriched in the RTK-RAS and Notch pathways. Hence, TMB could serve as a prognosis biomarker with potential clinical significance.

Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models.

Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles.

The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals.

The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models.

Natural biopolymers are used for various purposes in healthcare, such as tissue engineering, drug delivery, and wound healing. Bacterial cellulose and chitosan were preferred in this study due to their non-cytotoxic, biodegradable, biocompatible, and non-inflammatory properties. The study reports the development of a magnetic bacterial cellulose-chitosan (BC-CS-Fe3O4) nanocomposite that can be used as a biocompatible scaffold for tissue engineering. Iron oxide nanoparticles were included in the composite to provide superparamagnetic properties that are useful in a variety of applications, including osteogenic differentiation, magnetic imaging, drug delivery, and thermal induction for cancer treatment.

The magnetic nanocomposite was prepared by immersing Fe3O4 in a mixture of bacterial cellulose-chitosan scaffold and then freeze-drying it. The resulting nanocomposite was characterized using FE-SEM and FTIR techniques. The swelling ratio and mechanical strength of the scaffolds were evaluated experimentally. The biodegradability of the scaffolds was assessed using PBS for 8 weeks at 37°C. The cytotoxicity and osteogenic differentiation of the nanocomposite were studied using human adipose-derived mesenchymal stem cells (ADSCs) and alizarin red staining. One-way ANOVA with Tukey's multiple comparisons test was used for statistical analysis.

The FTIR spectra demonstrated the formation of bonds between functional groups of nanoparticles. FE-SEM images showed the integrity of the fibrillar network. The magnetic nanocomposite has the highest swelling ratio (2445% ± 23.34) and tensile strength (5.08 MPa). After 8 weeks, the biodegradation ratios of BC, BC-CS, and BC-CS-Fe3O4 scaffolds were 0.75% ± 0.35, 2.5% ± 0.1, and 9.5% ± 0.7, respectively. Magnetic nanocomposites have low toxicity (P < 0.0001) and higher osteogenic potential compared to other scaffolds.

Based on its high tensile strength, low water absorption, suitable degradability, low cytotoxicity, and high ability to induce an increase in calcium deposits by stem cells, the magnetic BC-CS-Fe3O4 nanocomposite scaffold can be a suitable candidate as a biomaterial for osteogenic differentiation.