Future Journal of Pharmaceutical Sciences最新文献

The expression patterns of T and B cell activation genes, along with Immunoglobulin G (IgG) subclasses, offer key insights into breast cancer progression. This study examined expression changes in four breast cancer subtypes - Luminal B HER2+, Luminal B HER2−, Luminal-like, and Triple Negative Breast Cancer (TNBC) - compared to healthy controls. Serum IgG subclass concentrations were also evaluated across these subtypes. Using the RT² Profiler QPCR array, expression of 84 genes was assessed, revealing 39 upregulated and 7 downregulated genes in Luminal B HER2+, 33 and 11 in Luminal B HER2−, 47 and 15 in Luminal-like, and 36 and 12 in TNBC, respectively. Four genes involved in antibody production were commonly altered across all subtypes. CD27 (P = 0.0122) showed fold changes of 5.60, 87.39, 49.93, and 109.38, while CD28 (P = 0.0014) increased by 54.13, 15.54, 26.95, and 54.41-fold. CD40 (P = 0.0003) was upregulated with 31.88, 15.28, 23.82, and 19.25 folds across subtypes, as was IL7 (P = 0.0002), with 2.89, 2.84, 3.52 and 3.28-fold increase. Conversely, LAG3 (P = 0.0347) was consistently downregulated (fold changes: 0.01, 0.01, 0.04 and 0.45). Immune checkpoint analysis revealed significant upregulation of CD274 (P = 0.0045), CD47 (P = 0.0432), CD276 (P = 0.0310) and TLR9 (P = 0.0081), while LAG3 (P = 0.0347) were significantly downregulated. ELISA-based serum analysis showed significantly elevated IgG1 across all subtypes (P < 0.007). IgG2 increased in Luminal B HER2− (P = 0.0007) and decreased in TNBC (P = 0.0004). IgG3 was reduced in Luminal B HER2+, Luminal-like, and TNBC (P < 0.035), while IgG4 increased in Luminal B HER2+ and HER2− but decreased in TNBC. These findings highlight pronounced, subtype-specific adaptive and innate immune responses in breast cancer, reflecting the intricate landscape of immune modulation in tumorigenesis.

Background

In this twenty-first century, artificial intelligence and computational-based studies, i.e., pharmaceutical biotechnology, are more important in every field, even in the field of drug discovery, design, and development, and they should be for managing time, cost, energy, and the environment, as well as chemical consumption in laboratories and research centers.

Main Body of the Abstract

The study of molecular docking with relative components like classifications, models, and different types of approaches and techniques involved, pose generation, scoring function advantages, disadvantages, and comparison with other types of docking tools to conduct the molecular docking with steps involved will be helpful to learn computer-aided drug design and artificial intelligence. The mechanism involved and the step-by-step procedure of molecular docking are well elaborated and understandable. The applications of molecular docking to finding new ligands and affinities, optimizing drug candidates, and understanding molecular interactions with different receptors like proteins and enzymes for the treatment of many diseases, viz. cancer, SARS-COVID, inflammation, gravis, glaucoma, Alzheimer’s disease, and bacterial infections, make it faster and cheaper than traditional screening. The almost or maximum molecular docking software, as applicable to the specialization in this study of drug discovery, design, and development, includes DOCK, GOLD, GLIDE, MOE, Schrödinger, FlexX, AutoDock, Hammerhead, AutoDock Vina, SwissDock, PyMol, MVD, BIOVIA, MEGADOCK, etc.

Short Conclusion

Overall, in the field of computational chemistry and pharmaceutical biotechnology, i.e., computational-aided drug design, molecular docking plays an important role in designing and developing a drug molecule to save time, cost, energy, and the environment. With its origins firmly rooted in the developments in computational chemistry and structural biology, molecular docking has evolved from a theoretical concept into an intricate and vital tool in contemporary drug discovery.

Background

Acne vulgaris is a prevalent inflammatory skin disorder marked by excessive oil production (seborrhea), follicular hyperkeratinization, bacterial proliferation (notably Cutibacterium acnes and Staphylococcus epidermidis), and inflammatory responses. Current treatments, including antibiotics, are increasingly challenged by rising resistance and adverse effects, emphasizing the need for safer, natural alternatives. The purpose of this study was to evaluate the antibacterial and anti-acne properties of pomegranate pericarp extract (PPE) and essential oils (EOs) of bitter orange, sweet marjoram, and tea tree.

Results

The chemical compositions of PPE and EOs were confirmed using advanced mass spectrometry techniques. Bitter orange oil, sweet marjoram oil, and PPE demonstrated superior antibacterial activity, as evidenced by larger zones of inhibition compared to reference antibiotics (clindamycin, erythromycin, and vancomycin). The minimum inhibitory concentrations (MICs) against C. acnes were 0.21 mg/mL for bitter orange oil, 0.44 mg/mL for sweet marjoram oil and tea tree oil, and 1.95 mg/mL for PPE. Against S. epidermidis, the MICs were 0.10, 1.75, 13.90, and 1.95 mg/mL, respectively. Synergistic antibacterial activity was observed when combining PPE with either bitter orange or sweet marjoram oil against C. acnes. Hence, two formulations with bitter orange oil (1.65 mg/g) and PPE (1.95 mg/g) were developed: regular gel (BOP) and nano-cubosomal gel (nBOP). Similarly, sweet marjoram oil (3.50 mg/g) and PPE (3.90 mg/g) were combined to create regular gel (MP) and nano-cubosomal gel (nMP). These formulations were tested in a C. acnes-induced inflammatory acne animal model to simulate the complex microbial, immune, and inflammatory interactions of acne pathogenesis. All developed herbal formulations exhibited in vivo anti-acne activities, demonstrated by the restoration of the normal histology of the mice ear tissue and a significant reduction in bacterial load, inflammation percent, and the inflammatory markers relative to the untreated group. However, nBOP showed the highest anti-inflammatory efficacy, followed by BOP; the difference in inflammation inhibition per cent between them (8.2%) was insignificant, suggesting that the regular gel may offer a cost-effective alternative without significantly compromising efficacy.

Conclusion

The study highlights the potential of combining bitter orange oil and pomegranate pericarp extract in a regular gel as a safe, natural, and affordable alternative for acne treatment.

Background

Benzimidazole, a fused heterocyclic compound, has emerged as a privileged structure in medicinal chemistry due to its broad spectrum of biological activities, particularly in antimicrobial and antitubercular (anti-TB) applications. Its structural ingenuity allows for diverse substitutions at key positions, facilitating interactions with various biological targets such as bacterial enzymes and nucleic acids.

Main body.

Benzimidazole derivatives have demonstrated potent activity against a wide range of Gram-positive and Gram-negative bacteria, as well as against Mycobacterium tuberculosis, including drug-resistant strains. The pharmacophoric features of benzimidazole contribute to its ability to inhibit vital microbial processes, including cell wall synthesis, DNA replication, and energy metabolism. Structural optimization of benzimidazole scaffold has led to the development of several lead compounds with enhanced efficacy and pharmacokinetic profiles.

Conclusion

This review highlights the significance of benzimidazole as a privileged scaffold in the development of novel antimicrobial and anti-TB agents, emphasizing recent advances in structure–activity relationship (SAR) studies, and potential for future drug development.

Background

To investigate medicinal plants used in the traditional treatment of cutaneous leishmaniasis using multivariate tests coupled with pharmacokinetic predictions in silico.

Main body

Interviews were conducted with 21 herbalists in Annaba and El Tarf provinces. The dataset comprised 26 variables, and multidimensional analyses were applied using the FactoMineR package. Nineteen species were reported in this survey. Among them, the most important family was Lamiaceae, with five species. According to the RFC index, the most famous species were the aerial parts of Teucrium polium L. (57.14%).

Second, a data matrix for the species generated showed higher contribution values in the first dimension owing to the lack of the topical administration form, the presence of preparation mode by decoction and cataplasm, and the association of medicinal plants specifically with olive oil and honey, respectively. The analysis of the first dimension demonstrated a high association for the form of administration and the mode of administration, with correlation ratios η² of 6.261E-01, 5.501E-01, and 4.772E-01 (p < 0.05), respectively. The cluster analysis identified three clusters differentiated by the administration form per os with a p-value of 7.49E-05 (p < 0.05). Later, the ADME profile was tested in silico by identifying the physicochemical properties of the major compounds reported in the literature.

Conclusions

The results showed that the major compounds of plants with high RFC showed excellent ADME profiles, with good absorption, low toxicity, and favorable distribution, making them promising candidates for the safe treatment of leishmaniasis.

Background

The conventional drug delivery devices always present a “one-size-fits-all” approach which limits their application in pharmaceutical industry, because of their inability to adapt to individual pharmacokinetic features. Three-dimensional (3D) printing is the most economical substitutes for transferring from the “one-size-fits-all” approach (i.e., mass production) to fabricate small individualized batches.

Main text

3D printing, advanced by the additive manufacturing technology, has gained growing demanding and popularity to develop pharmaceutical dosage forms and medical devices; and offered much more preferences over the traditional fabrication technologies. This advanced technology presents the ability of fabricating customizable design, 3D structures with sophisticated architecture, intended for personalized treatment. As a further advancement, the emergence of four-dimensional (4D) printing extensively contributed to the advancement of personalized medication by combining the benefits of smart multiple functional materials with the 3D printing technology. In spite of all of the offered notable progresses in both techniques, some regulatory issues, scalability, and production cost present key obstruction.

Conclusions

In the present article, an overview on the latest research articles demonstrating some step forward accomplishments for exploiting 3D and 4D printing technologies in developing advanced pharmaceutical dosage forms, medical devices, and tissue engineering as well as presenting the foremost challenges and future perspectives.

Graphical abstract

Background

Cardiac remodeling post-myocardial infarction contributes to adverse outcomes and increased mortality. We aimed to evaluate the impact of Dapagliflozin on remodeling markers, clinical outcomes and quality of life of diabetic ST-elevation myocardial infarction (STEMI) patients. This was an open label, single centered, randomized controlled-clinical trial was conducted at the Cardiology department, Ain Shams University. Eligible diabetic STEMI patients (n = 54) were randomly allocated to receive either 10 mg of dapagliflozin plus standard of care (Test group) or standard of care alone (Control group) for 4 weeks. The primary outcome was to assess the changes in suppression of tumorigenicity 2 (sST2) over time. Secondary outcomes included: echocardiographic evaluations (left ventricular ejection fraction (LVEF), End Diastolic Diameter (EDD), End systolic volume (ESV), End diastolic volume (EDV) and quality of life using EQ-5D-5L questionnaire.

Results

No change was observed in sST2 levels either between or within groups from baseline to 4 weeks. Echocardiographic and quality of life parameters were comparable between groups after 4 weeks. LVEF was significantly increased in the study group at the end of study (42 vs. 47, P < 0.001).

Conclusions

Early administration of dapagliflozin in post-MI diabetic patients had no effect on sST2 and quality of life but improved LVEF after 4 weeks of follow up. More studies are needed with larger sample sizes to further investigate SGLT2-inhibitors potential benefits in such population.

ClinicalTrial.gov registration number: NCT05335629

Neurodegenerative disorders, a group of diseases such as Alzheimer’s and Parkinson’s diseases, are identified by gradual memory and motor impairment, thus, seriously affecting aging populations. New research brings a paradigm shift in the pathogenesis of these conditions by identifying gut microbiota as a fundamental factor owing to dysbiosis through microbiota-induced neuroinflammation. Besides, the gut microbiome, referred to as dysbiosis, is exclusively responsible for activating the immune system thereby causing neuroinflammation, something that leads to breakdown of the blood–brain barrier and accumulation of toxic protein aggregates, such as amyloid-beta and alpha-synuclein. The gut-brain axis stays in the way of the advancement of such diseases, provided it allows for the necessary biochemical and immunity links. Microbial short-chain fatty acids (SCFA) and other metabolic by-products that are produced by these microbes either increase or decrease the stability of the central nervous system, while reduced SCFA production caused by dysbiosis, however, brings about neuroinflammation. From this perspective, the microbiota-gut-brain connection serves as a novel source for innovation in disease cure, including probiotics, prebiotics, dietary modifications, as well as the microbiota fecal transplant, restoring the microbial balance and thus, alleviating the disease progression. This examination establishes the current role of the microbiota in neurodegeneration and potential microbiome-focused treatments for neuroprotection.

Background

Acinetobacter baumannii, a nosocomial pathogen, has emerged as a major clinical threat due to its ability to resist a broad range of antibiotics, contributing to the increased morbidity and mortality in hospital settings. This characteristic of Acinetobacter baumannii as a multiple-drug resistant (MDR) organism poses a critical global health challenge, necessitating an urgent need for alternative therapeutic strategies, such as vaccine development, as a preventive measure. In this study, we employ the method of reverse vaccinology and immunoinformatic tools to design a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii.

Results

16S and 23S rRNA sequences of Acinetobacter baumannii were retrieved from the National Center for Biotechnology Information database (NCBI). The B and T cells’ epitopes were predicted from these retrieved sequences using bioinformatics tools. The epitopes generated were further analyzed for antigenicity, toxicity, and allergenicity. The epitopes that passed these screenings, including key structural elements, were used in the design of the vaccine. The vaccine constructs were further assessed for their physicochemical properties and dynamics. Structural modeling and molecular docking studies confirmed effective binding to Toll-like receptor 4 (TLR-4), while immune simulations demonstrated the potential to elicit robust and durable immune responses.

Conclusions

This study demonstrates the potential of reverse vaccinology and immunoinformatics approaches in designing a novel rRNA-based vaccine targeting the 16S and 23S rRNA of Acinetobacter baumannii. By identifying highly antigenic, non-toxic, and non-allergenic epitopes and incorporating them into a structurally optimized rRNA-based vaccine construct, we present a promising candidate capable of eliciting strong immune responses. However, limitations such as the unavailability of datasets, especially on the 5S rRNA region in the databases, are a roadblock that needs to be addressed.

Background

Patients with chronic diseases often have difficulties in managing multiple medications, resulting in poor adherence and, subsequently, adverse health consequences. Extensive research has demonstrated the beneficial effects of medication management devices, such as pill box organizers (PBOs) on enhancing medications adherence and improving patients’ health outcomes. However, research on PBOs in Egypt is limited. This study seeks to assess the awareness, user satisfaction of PBOs and their influence on medication adherence among Egyptian people with chronic illnesses.

Methods

Fifty -six Egyptian adults participated in a prospective observational study. Participants were recruited from two locations: a university employee and community individuals. Participants were asked to use a pillbox organizer for three months. Demographic data were gathered at baseline. During a bi-weekly interviews, we calculated missing doses for the past two weeks. At the end of the study period, a questionnaire containing yes/no questions to assess patients' awareness and PBO feasibility was conducted. The acceptability, usability, medication management support, and satisfaction of patients with the device were evaluated using a Likert scale.

Results

Sixty-one percent of the participants were aged 50 years or older. Almost 66% individuals possessed no prior awareness of pillbox organizers (95% CI: 0.54, 0.78, p = 0.0162). Nearly 90% deemed PBO beneficial for drug adherence (95% CI: 0.95, 1.02, p = 0). Most of the participants (80%) believed the PBO user-friendly, while 89% indicated that the device assisted in reminding them to adhere to their prescription regimen. The mean satisfaction score was 4.02 (± 0.25) on a 5-point Likert scale. Ninety-one percent of interviewees indicated that they would acquire a PBO if required.

Conclusion

The study participants viewed the PBO as an acceptable and useful tool for managing multiple medications, despite their limited awareness of them. The higher satisfaction and perceived usefulness indicate the feasibility for using PBOs in the Egyptian healthcare environments as well as its impact in enhancing drug adherence. Future research could focus on evaluating long-term adherence and health outcomes.