Future Journal of Pharmaceutical Sciences最新文献

Background

Enterococci, known for their disturbing involvement in nosocomial infections, possess a diverse set of virulence factors, regulated by multiple genes. A key virulence regulator is the fecal Streptococcus regulator (Fsr) quorum sensing system. Multiple reports describe the involvement of fsr genes in several virulence mechanisms, notably gelatinase production and biofilm formation; however, the presence of fsr genes does not necessarily predict those virulence phenotypes. This study investigates the factors affecting the relation between molecular detection of fsr genes and accurate prediction of gelatinase activity and biofilm formation intensity.

Methods

One hundred enterococcal samples were collected from patients suffering from urinary tract infections. The isolates were identified through the use of a polymerase chain reaction (PCR) technique targeting the ddl gene. Biofilm formation was quantified by the crystal violet assay, while gelatinase activity was evaluated on gelatin agar plates. PCR was used to detect the fsrA and fsrB genes, as well as the gelatinase enzyme-encoding gene (gelE).

Results

Out of the collected 100 isolates, 93% were identified as Enterococcus faecalis. The isolates formed biofilm with different intensities: 47% were strong biofilm producers, 28% moderate, and 21% weak, while only four isolates (4%) did not form biofilm. Only 14% of all isolates had detectable gelatinase activity. The fsrA and fsrB genes were detected in 26% and 28% of the tested isolates, respectively, while gelE was detected in 57% of the isolates. Whereas no association was found between biofilm formation intensity and fsr locus genes or gelatinase activity, a strong positive correlation (r = 1) was found between the detection of both fsrA and fsrB genes and the gelatinase activity.

Conclusion

fsrA and fsrB have a diagnostic value and may be used as biomarkers for gelatinase activity in E. faecalis.

Background

Atrial fibrillation (AF) is the most prevalent cardiac condition linked to increased mortality due to complications such as stroke. Oral anticoagulant (OAC) is the mainstay in preventing cerebrovascular accidents in patients with AF. Recent evidence identified gaps in physician’s knowledge in diagnosing and managing patients with AF. This study aims to assess Syrian physicians’ knowledge, attitude, and practices regarding the use of anticoagulant therapy in non-valvular AF (NVAF) patients. A cross-sectional study was conducted using a validated web-based questionnaire, which included 56 items separated into four sections that collected information about demographics, knowledge, attitude, and practices. Chi-square and Kruskal Wallis were performed to analyze the statistical relationships between the knowledge, attitude, practice, and demographic variables.

Results

A total of 497 participants completed the survey, of which 62.6% were between the ages of 25 and 35. The average participant scores for knowledge, attitude, and practices were (48.18 ± 21.57), (81.54 ± 9.26), and (62.83 ± 12.42), respectively. Participants who demonstrated good understanding, a positive attitude, and good practices were 22.3%, 87.3%, and 25.4%, respectively. The fear of bleeding was identified as the most significant barrier to initiating anticoagulant medication in AF patients (55.5%). Doctors who attended training had a better knowledge score than those who did not (mean ± S.D. = 57.24 ± 20.7). Participants who stated that over 70% of their AF patients use aspirin received the highest attitude score (mean ± S.D = 86.98 ± 21.17). PhD participants reported higher practice scores than those with other educational backgrounds (mean ± S.D = 73.96 ± 11.3).

Conclusion

This research showed that primary care physicians in Syria had optimistic views regarding OAC therapy, suggesting that training interventions targeting physicians may lead to improvement in the treatment of patients with NVAF in Syria.

Background

A common condition known as endometriosis typically takes place in females in their reproductive age and develops generally in the endometrial lining of females. Chronically, endometriosis has been associated with a reduction in the patient’s quality of life (QOL) which can have a hazardous impact on their social working and functionality. Owing to the involvement of hormones in the development of endometriosis, drugs having the capability to modulate the hormonal concentrations, along with surgical techniques, have been designed to treat endometriosis.

Main body

There are certain drawbacks of the currently existing therapy for endometriosis which include the inability to improve the quality of life of the patient, treatment failures and unresponsiveness from the patient, and adverse effects of the drugs such as weight gain, mood swings, vaginal dryness, etc. Herbal medicines have attracted the attention of various researchers for the development of novel therapeutics against several gynecological disorders, mainly endometriosis. Our present review summarizes the precise pathogenesis of endometriosis along with its conventional therapy and novel developments in herbal medicines wherein we have compiled data from 15 completed clinical trials (conventional therapy: 7, herbal therapy: 8). Additionally, we have included data from four preclinical studies on herbal medicine that showed promising results in treating endometriosis highlighting the necessity for clinical trials to yield more definitive findings. The number of clinical trials carried out to assess the response of herbs in endometriosis is limited which is why additional studies could provide beneficial concrete evidence in the effective treatment of endometriosis and ensure improved patient outcomes.

Conclusion

Conventional therapies possess certain limitations to treat endometriosis due to which the attention of scientists has shifted toward herbal therapy due to its advantages such as improved safety and tolerability in treating endometriosis. However, additional clinical investigations into herbal therapy may prove to be fruitful in the discovery of novel therapeutics to treat endometriosis effectively.

Background

There is a soar in the figure of companies aiming to achieve efficiency in undergoing experimental processes. Therefore, instead of deploying one-factor-at-a-time, design of experiments is becoming rampantly utilized in order to reduce the resources outflow. There are a copious of different smart designs which could be employed as design of experiments tools. Central composite and d-optimal designs were investigated in this paper. The purpose of this investigation was to compare the two designs and identify the most accurate design at analyzing, interpreting and making predictions with regards to the data offered. The aforementioned purpose was achieved by applying both designs to a preexisting study which sought to prolong the gastrointestinal retention of repaglinide tablets through deploying a full factorial design. Further optimization was performed using Design-Expert software after inducing an outlier point.

Results

R-squared, adjusted R-squared, predicted R-squared and adequate precision were computed in addition to acquiring diagnostics figures such as predicted versus actual, residual versus run, Box–Cox, contour plot and 3D surface plots. Model equations were also produced for each design. Results showed that both designs were successful at modeling the data both scoring r-squared values > 0.7 and adequate precision > 4 implying high fitting, prediction power and ability to navigate the experimental space using a reduced number of experimental runs. The d-optimal design obtained the least relative error of only 3.81%.

Conclusions

In conclusion, the d-optimal design provides a great tool for reduction of experimental testing which in turn diminishes resources consumption. Therefore, this design is favored to be enforced in the pharmaceutical sector.

Backgrounds

The overall survival of patients with lower-grade gliomas and glioblastoma varies greatly. No reliable or existing procedures can accurately forecast survival and prognostic biomarkers for early diagnosis in glioma and glioblastoma. However, investigations are progressing in immunotherapy, tumor purity, and tumor microenvironment which may be therapeutic targets for glioma and glioblastoma.

Results

This study indicated the possible prognostic signatures that can be used to identify immune-related prognostic biomarkers in the prediction of the survival of low-grade glioma (LGG) patients which may be a possible therapeutic target. In addition, the Kaplan–Meier plot, ESTIMATE algorithm, and TIMER 2.0 analysis indicated that Krüppel-like factor 15 (KLF15) p = 0.030, Aquaporin 7 (AQP7) p = 0.001, and Human 1-acylglycerol-3-phosphate O-acyltransferase 9 (AGPAT9) p = 0.005 are significantly associated in glioma. Hence, they may be possible prognostic biomarkers in glioma. Meanwhile, in the glioblastoma, only KLF15 has a significant association with glioblastoma (p = 0.025). Stromal and immune scores of gliomas were determined from transcriptomic profiles of LGG cohort from TCGA (The Cancer Genome Atlas) using the ESTIMATE (Estimation of Stromal and Immune cells in Malignant Tumours using Expression data algorithm). The immune infiltration of the KLF15, AQP7, and AGPAT9 for low-grade glioma and glioblastoma was determined using TIMER immune 2.0 which indicates correlation with tumor purity for KLF15, AQP7, and AGPAT9, but only KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively.

Conclusions

These results highlight the significance of microenvironment monitoring, analysis of glioma and glioblastoma prognosis, and targeted immunotherapy. To our knowledge, this is the first time to investigate an analysis that revealed that KLF15, AQP7, and AGPAT9 may be important prognostic biomarkers for patients with glioma and KLF15 for patients with glioblastoma. Meanwhile, KLF15 and AGPAT9 are significantly associated in both glioma and glioblastoma, respectively, for tumor purity.

Background

The current investigation aimed to develop, optimise, and assess a mupirocin-loaded nanosponge-based topical delivery system for diabetic foot ulcer and to achieve prolonged drug release while improving drug deposition within the skin. The nanosponges carrying mupirocin were formulated using the emulsion solvent diffusion method. A 3² factorial design was utilised to investigate effect of two factors, specifically the concentration of ethyl cellulose and the stirring rate, on the physical attributes of the nanosponges. The optimised nanosponge formulation batch (F9) was subsequently incorporated into a Carbopol gel base, ensuring the desired physical attributes were achieved in the gel formulation containing nanosponges. The research included in vitro drug release evaluation, ex vivo drug deposition analysis, assessment of the antimicrobial action of the nanosponge formulation, and in vivo diabetic wound healing.

Results

Drug polymer compatibility analysis was conducted using FT-IR spectroscopy revealed no interactions among mupirocin and ethyl cellulose molecules. Further FT-IR spectroscopy, DSC spectroscopy, and XRD spectroscopy analysis of optimised formulation batch revealed that the drug was successfully entrapped in nanosponges. Scanning electron microscopy confirmed the spherical and porous nature of the prepared nanosponges. The drug release pattern across the cellulose dialysis membrane followed a diffusion-controlled release pattern, and the drug deposition analysis exhibited substantial retention of mupirocin in the skin from the nanosponges formulation for up to 24 h. Furthermore, the optimised nanosponges gel formulation demonstrated stability and non-irritant properties, as indicated by the HET-CAM test. In vivo evaluation of wound healing activity in a Streptozotocin-induced diabetes mellitus with excision wound model revealed significant actions pertaining to wound healing and closure after 16 days of treatment.

Conclusion

The mupirocin-loaded nanosponge gel contributed to remarkable and swift recovery and closure of wounds in diabetic rats. The nanosponges, acting as carriers for mupirocin, facilitated the effective delivery of the drug to the wound area, while the gel fostered an optimally humid environment conducive to wound care during the final stages of wound healing and sealing.

Graphical abstract

Objective

Biopharmaceutics Classification System says that simvastatin (SMV) is a Class II drug with low bioavailability (5%). This is because it dissolves slowly and is broken down a lot in the first pass. Simvastatin transdermal patches were produced as part of this study's aim to treat hyperlipidemia. The Box–Behnken design (three-factor, three-level) was selected for optimization of patches.

Methodology

The optimization design involved 15 runs with independent factors hydroxypropyl methylcellulose K100, Eudragit L100, and polyethylene glycol 400 percentage, and dependent factors including folding endurance and in-vitro drug release.

Results

The results showed that the concentration of hydroxypropyl methylcellulose K-100 positively impacted the patch’s folding endurance. The fact that factor C was the only scenario where the p-value was less than 0.05 and the coefficient value was higher in the in vitro drug release model means that it has a greater influence on the release of medicines. The patches were also evaluated for drug content, swelling, moisture uptake, moisture content, etc. The optimized patch shows an in vitro drug release of 55.3% in up to 24 h. In vivo antihyperlipidemic activity was evaluated in albino Wistar rats. In the standard treatment (simvastatin oral) groups, there is a decrease in cholesterol (132.76 ± 0.35) and triglyceride level (139.80 ± 76) whereas in the test formulation group or test group, there is also a decrease in cholesterol (169.65 ± 0.21 mg/dL) and triglyceride level (151.20 ± 31 mg/dL) level.

Conclusion

Based on in-vitro and in-vivo results it can be concluded that simvastatin patches can be an alternative to traditional therapy.

Background

Intervertebral disc degeneration (IVDD) is a prevalent condition known to contribute to lower back pain and various spinal disorders. The progression of IVDD is closely associated with cell ferroptosis. This study aimed to explore the therapeutic potential of a reactive oxygen species (ROS)-responsive hydrogel loaded with garlic extract for the inhibition of cell ferroptosis and the treatment of IVDD.

Results

The study encapsulated garlic extract within the hydrogel using physical entrapment and controlled the release of the extract through the ROS-responsive degradation of the hydrogel. Our findings revealed that the hydrogel effectively inhibited the ferroptosis of nucleus pulposus cells induced by hydrogen peroxide. Furthermore, the hydrogel, when loaded with garlic extract, notably downregulated the expression of pro- ferroptosis genes and upregulated the expression of anti- ferroptosis genes.

Conclusions

This study demonstrated that the hydrogel loaded with garlic extract significantly mitigated IVDD. These results highlight the promising potential of ROS-responsive hydrogel loaded with garlic extract as a viable treatment option for addressing IVDD.

Background

The Junín virus (JUNV) is well known for causing argentine haemorrhagic fever (AHF), a severe endemic disease in farming premises. The glycoprotein of JUNV is an important therapeutic target in vaccine design. Despite using drugs and neutralizing weakened antibodies being used in the medication, neither the severity reduced nor eradicated the infection. However, this constraint can be resolved by immunoinformatic approaches.

Results

The glycoprotein fasta sequence was retrieved from NCBI to anticipate the B cell and T cell epitopes through the Immune Epitope Database. Furthermore, each epitope underwent validation in Vaxijen 2.0, Aller Top, and Toxin Pred to find antigenic, nonallergic, and non-toxic peptides. Moreover, the vaccine is designed with appropriate adjuvants and linkers. Subsequently, physicochemical properties were determined in ProtParam including solubility and disulphide bonds in the SCRATCH server. The vaccine 3D structure was built using I-TASSER and refined in ModRefine. Docking between JUNV glycoprotein (PDB ID:5NUZ) with a built vaccine revealed a balanced docked complex visualized in the Drug Discovery studio, identified 280 hydrogen bonds between them. The docking score of − 15.5 kcal/mol was determined in the MM/GBSA analysis in HawkDock. MD simulations employed using the GROMACS at 20 ns resulted in minimal deviation and fewer fluctuations, particularly with high hydrogen bond-forming residues.

Conclusion

However, these findings present a potential vaccine for developing against JUNV glycoprotein after validating the epitopes and 3D vaccine construct through in silico methods. Therefore, further investigation in the wet laboratory is necessary to confirm the potentiality of the predicted vaccine.

Background

Diabetes is one of the most prevalent metabolic diseases with high rate of morbidity and mortality. The increased level of blood glucose level and increased insulin resistance is the hallmark of diabetes. Currently, various non-pharmacological and pharmacological therapeutic options are used for lowering the glucose level and improving the insulin activity. The current systematic review and meta-analysis study was conducted to evaluate the efficacy of Berberis aristata and Silybum marianum fixed dose nutraceutical combination on serum glucose and glycated haemoglobin level and insulin resistance parameters.

Main Body

Randomized controlled trials, identified from three online databases, evaluating the efficacy of Berberis aristata and Silybum marianum fixed dose combination were identified and evaluated as per pre-defined protocol. Quality of studies was evaluated using PEDro scale, and risk of bias was assessed using Cochrane Risk of Bias Tool. Pooled effect was reported as mean difference (MD) and 95% confidence interval, while the complete study was conducted as per PRISMA and Cochrane guidelines. After complete literature screening and evaluation process, seven studies were included in the final analysis. Data of 825 participants (active group: 416 participants and control group: 409 participants) were utilized for the statistical analysis. All included studies (except one) were of good quality. Supplementation of fixed dose combination significantly reduced glucose level (MD: − 5.26 mg/dl; p = 0.02) and glycated haemoglobin (HbA1c) level (MD: − 0.69%; p < 0.0001) as compared to control therapy, while greater insulin resistance reduction was observed in active group and the difference approached significance (MD: − 0.64 HOMA-IR score; p = 0.08). Risk of bias analysis revealed some concerns regarding biasness (mainly due to randomization, outcome measurement and selected reporting biasness). All included studies had moderate risk of biasness. Sensitivity analysis revealed effect of particular study on overall heterogeneity observed, while neither significant publication bias nor any missing study was observed.

Conclusion

The results of current study suggest that B. aristata and S. marianum fixed dose combination is effective in improving glycaemic and insulin parameters and can be effective in diabetic population. The observed sensitivity of certain studies on overall heterogeneity and the moderate risk of biasness warrants further well-designed clinical studies to strengthen the results of current study.