Current pharmaceutical biotechnology最新文献

Skin cancer, which comprises both melanoma and non-melanoma forms, is frequently diagnosed as the predominant malignancy among today's population. Existing treatments are often prolonged and complex, have a low rate of success, and have side effects. This complexity leads to poor patient adherence and increases the risk of disease recurrence. Ethosomes, extensively studied for their applications in topical and transdermal therapies, are distinguished by their high ethanol content, which facilitates enhanced skin penetration and efficient drug delivery. Compared to traditional liposomes, ethosomes offer notable advantages due to their unique composition, demonstrating potential efficacy in treating various skin conditions, including basal cell carcinoma, squamous cell carcinoma, and melanoma. The present review provides a brief introduction to skin melanoma and its pathogenesis, signalling pathways, biomarkers, the need for ethogel-based drug delivery, applications of ethosomes against skin cancer, and clinical trials.

Fungal infections contribute to over 1.5 million fatalities each year, with cutaneous mycoses standing as prominent global infections. The spectrum of these mycoses varies widely, encompassing enduring afflictions like ringworm, localized infections such as tinea capitis, recurrent instances like vaginal candidiasis, and potentially fatal systemic infections impacting multiple organ systems. The escalating recognition of the health and socioeconomic ramifications associated with fungal pathogens underscores their importance in contemporary discourse. On a global scale, projections indicate that over 300 million individuals experience significant fungal infections annually, resulting in a mortality rate exceeding 1.5 million deaths per year. Alarmingly, resistance to commonly used antifungal drugs was on the rise, with some reports suggesting that over 10% of Candida bloodstream isolates worldwide were resistant to fluconazole, a commonly prescribed antifungal medication. Therefore, there is an immediate need to increase the accessibility of new antifungal medications while minimizing their costs and adverse effects. Fungi, as heterotrophic organisms, acquire nutrients through absorption. Their filamentous structure, composed of hyphae, facilitates efficient nutrient uptake by secreting enzymes that break down complex organic matter into simpler compounds. These organisms exhibit remarkable adaptability in responding to environmental cues, adjusting growth rates, and altering morphological features. Fungi regulate their metabolism intricately, undergoing various metabolic pathways for energy production and utilizing diverse substrates for respiration. Additionally, they exhibit distinctive reproductive strategies, employing both sexual and asexual modes of reproduction, contributing to their genetic diversity and resilience in diverse ecosystems. We now have more information than ever on the origins of infection as well as the physiology of fungi cells, giving us the chance to use it to produce new generations of antifungals. This review includes various novel antifungal drug targets showing their possible effects via different mechanisms aiming at vital functions like GPI synthesis, cell wall synthesis, hyphal growth, and other essential pathways responsible for fungal growth.

Background: Previous studies have demonstrated that TRIB3 plays a carcinogenic role in tumor progression. However, the exploration of TRIB3 at the pan-cancer level has not been reported.

Aims: This study aimed to conduct a comprehensive pan-cancer analysis of TRIB3.

Objective: We explored the expression pattern and functional mechanism of TRIB3 on the basis of multiple databases.

Method: We first explored the expression level of TRIB3 in the TCGA database. Then, the receiver operation characteristic curve (ROC), Kaplan-Meier plotter, and Cox regression were used to estimate the diagnostic and prognostic value of TRIB3, respectively. We also explored the relationship between TRIB3 and the infiltration of tumor immune cells, as well as the expression of immune checkpoint molecules. Gene enrichment and protein interaction network analysis were carried out to identify possible carcinogenic molecular mechanisms and functional pathways. Finally, we compared the non-promoter region methylation of TRIB3 in normal and tumor tissues and explored potential systems with unique functions in TRIB3-mediated tumorigenesis.

Result: The expression level of TRIB3 was elevated in multiple tumor types, and the high expression of TRIB3 was associated with poor prognosis. TRIB3 had a higher frequency of genetic changes in several tumors and showed varying trends in TRIB3 methylation levels. Additionally, high expression of TRIB3 was also associated with infiltration of cancer-related fibroblasts and different types of immune cells and was positively correlated with the expression of immune checkpoint molecules. Furthermore, gene enrichment analysis suggested that TRIB3 may play a role in the malignant progression of cancer by participating in protein post-translational modifications and activating transcription initiation factors.

Conclusion: Our pan-cancer analysis provided the potential carcinogenic role of TRIB3 in tumors and verified a promising target for clinical immune treatment.

Background: Leishmaniasis is responsible for approximately 65,000 annual deaths. Various Leishmania species are the predominant cause of visceral, cutaneous, or mucocutaneous leishmaniasis, affecting millions worldwide. The lack of a vaccine, emergence of resistance, and undesirable side effects caused by antileishmanial medications have prompted researchers to look for novel therapeutic approaches to treat this disease. Antimicrobial peptides (AMPs) offer an alternative for promoting the discovery of new drugs.

Methods: In this study, we detail the synthesis process and investigate the antileishmanial activity against Leishmania (Viannia) braziliensis for peptides belonging to the dermaseptin (DS) family and their synthetic analogs. The MTT assay was performed to investigate the cytotoxicity of these peptides on the murine macrophage cell line RAW 264.7. Subsequently, we performed molecular modeling analysis to explore the structure-function correlation of the derivatives interacting with the parasitic membrane.

Results: All examined derivatives displayed concentration-dependent antileishmanial effect at low concentrations. Their effectiveness varied according to the peptide's proprieties. Notably, peptides with higher levels of charge demonstrated the most pronounced activities. Cytotoxicity assays showed that all the tested peptides were not cytotoxic compared to the tested conventional drug. The structure-function relationships demonstrated that the charged N-terminus could be responsible for the antileishmanial effect observed on promastigotes.

Conclusion: Collectively, these results propose that dermaseptins (DS) might offer potential as promising candidates for the development of effective antileishmanial therapies.

Background: Immunotoxins (ITs) represent a novel class of therapeutics with bifunctional structures that facilitate their penetration through cell membranes to induce target cell destruction. Programmed cell death ligand-1 (PD-L1), a human cell surface protein, is overexpressed in various cancers. This study aimed to construct a novel IT by genetically fusing an anti-PD-L1 Nanobody (Nb) to a truncated diphtheria toxin (DT).

Methods: The IT construct comprised a 127-amino acid anti-PD-L1 Nb fused to a 380-amino acid fragment of DT, with an N-terminal 6x-His tag. Molecular cloning techniques were employed, followed by transformation and verification through colony-PCR, enzyme digestion, and sequencing. The anti-PD-L1 Nb was expressed in WK6 E. coli cells induced by Isopropyl β-D-1- Thiogalactopyranoside (IPTG) and purified from periplasmic extracts using immobilized Metal Ion Affinity hromatography (IMAC). The IT was similarly expressed, purified, and validated via SDS-PAGE and Western blot analysis.

Results: ELISA confirmed the binding activity of both Nb and IT to immobilized PD-L1 antigen, whereas truncated DT exhibited no binding. MTT assays demonstrated significant cytotoxicity of IT on A-431 cell lines compared to Nb and truncated DT controls. Statistical analyses underscored the significance of these findings.

Conclusion: This study provides a thorough characterization of the constructed IT, highlighting its potential as a therapeutic agent targeting PD-L1-expressing cancer cells. The results support the potential of this IT in cancer immunotherapy, emphasizing the need for further investigation into its efficacy and safety profiles.

The human microbiota represents the community and diverse population of microbes within the human body, which comprises approximately 100 trillion micro-organisms. They exist in the human gastrointestinal tract and various other organs and are now considered virtual body organs. It is mainly represented by bacteria but also includes viruses, fungi, and protozoa. Although there is a heritable component to the gut microbiota, environmental factors related to diet, drugs, and anthropometry determine the composition of the microbiota. Besides the gastrointestinal tract, the human body also harbours microbial communities in the skin, oral and nasal cavities, and reproductive tract. The current review demonstrates the role of gut microbiota and its involvement in processing food, drugs, and immune responses. The discussion focuses on the implications of human microbiota in developing several diseases, such as gastrointestinal infections, metabolic disorders, malignancies, etc., through symbiotic relationships. The microbial population may vary depending on the pathophysiological condition of an individual and thus may be exploited as a therapeutic and clinical player. Further, we need a more thorough investigation to establish the correlation between microbes and pathophysiology in humans and propose them as potential therapeutic targets.

Background: Guettarda viburnoides Cham. & Schltdl., "veludinho do campo", is used in the Brazilian Amazon for its effects on the central nervous system (CNS) as a "brain tonic"; however, scientific evidence is needed to elucidate its ethnobotanical uses.

Objective: This study evaluated the neurobehavioural effects of an ethanolic extract of G. viburnoides (EEGV). Molecular docking, microchemical and morphoanatomical features of the species were investigated.

Methods: EEGV was investigated by UHPLC‒MS/MS and dereplication and molecular network were investigated using platforms available for natural product chemistry. For the in vivo assay, EEGV was administered to mice orally (3, 30 or 100 mg/kg). The effect of EEGV on spatial memory was measured using the Morris water maze test in mice with scopolamine-induced amnesia. The depression- and anxiety-like effects were assessed by forced swimming, tail suspension, marble burying and elevated plus maze tests. The AChE inhibition was evaluated in the brains of treated mice and molecular docking simulations were carried out with the main constituents. The leaves and stems of G. viburnoides were analysed via optical microscopy, scanning electron microscopy and energy dispersive X-ray spectroscopy.

Results: Secoxyloganin, grandifloroside, hyperin/or isoquercitrin, uncaric acid and ursolic acid were identified by UHPLC‒MS/MS. Molecular networking by three flavonoids, three triterpenes, two coumarins, two iridoids, and one phenolic acid. EEGV reversed these scopolamineinduced effects. In the forced swim and tail suspension test, EEGV (30 and 100 mg/kg) significantly reduced the immobility time. EEGV significantly reduced the number of buried marbles, while in the elevated plus maze test, no changes were observed compared to the Sco group. AChE activity was altered in the hippocampus. Studies of the molecular coupling of iridoid glycosides (grandifloroside and secoxyloganin) and flavonoid hyperin with AChE revealed significant interactions, corroborating the activity indicated by the inhibition assay.

Conclusions: These results might be in accordance with medicinal use for neuroprotetor effects and important microchemical and micromorphological data that support the identification and quality control of G. viburnoides.

Introduction: Honey possesses several positive properties, making it effective in wound healing mechanisms. However, very little information is available on the different honey types for wound healing activity.

Method: In the first "Academy of Sciences", a public engagement project with high school students, we assessed the properties of thirteen kinds of honey from the Piedmont area (Nord West Italy). In particular, we characterized the color intensity (by Pfund scale), total phenolic content (TPC), total flavonoid content (TFC), H2O2 production, and wound closure rate.

Results: Then, we tried to verify the presence of a correlation between these parameters, finding a positive correlation between H2O2 and wound closure rate.

Conclusion: These data pave the way to characterize different types of Italian honey to completely understand its potential.

Background: Organophosphorus insecticides, widely used in farming and agriculture, have been associated with various health issues. Curcumin, a natural antioxidant, has shown potential in mitigating the adverse effects induced by these insecticides.

Aim: This study aimed to evaluate the nephroprotective effects of Curcumin (CUR) against Chlorpyrifos (CPF)-induced renal damage.

Method: Forty male Wistar albino rats were randomly assigned to five groups, each containing eight rats: control (0.5 mL of olive oil, the solvent for chlorpyrifos), CPF (10 mg/kg of chlorpyrifos), CPF + CUR 25 mg/kg/day, CPF + CUR 50 mg/kg/day, and CPF + CUR 100 mg/k/day. All groups were treated for 90 days. Finally, kidney tissue was assessed for oxidative stress, inflammatory markers, and histopathological changes.

Result: A considerable elevation in urea and Creatinine (Cr) concentrations was observed in the CPF group compared to the control rats (p < 0.01). CUR decreased creatinine and urea levels in the CPF-exposed group compared to the non-CUR-treated animals (p < 0.05). Additionally, the concentrations of NO, MDA, IL-6, IL-1β, and TNFα were significantly increased in the kidneys of the CPF-induced rats compared to the controls (p < 0.001). However, CUR (100 mg/kg) administration significantly reduced the abovementioned parameters in rat kidneys (p < 0.01). CUR (100 mg/kg) also increased superoxide dismutase activity and glutathione concentration in the kidneys of CPF-exposed animals compared to non-CUR-treated rats (p < 0.05). Histopathological analysis revealed severe congestion in the kidney tissue after CPF exposure. However, coadministration of CUR restored the normal structure of the kidney in the experimental rats.

Conclusion: Our findings suggest that curcumin, a potent antioxidant, can help alleviate chlorpyrifos-induced nephrotoxicity.