Beni-Suef University Journal of Basic and Applied Sciences最新文献

Background

The lungs serve a critical function in air transport and gas exchange, presenting an appealing route for noninvasive drug administration. However, the unique physiology and anatomy of the lungs influence the efficacy and safety of pulmonary drug delivery. A comprehensive approach combining both an optimized pharmaceutical formulation and an appropriate delivery device is essential for effective pulmonary therapies.

Main body

Pulmonary drug delivery can achieve both local and systemic effects. During pulmonary drug delivery, several factors viz. particle size, electrostatic charge, inhalation parameters, airway functionality, disease state, and proper use of delivery device must be considered. Current advancements in nanotechnology have led to the development of innovative nanocarriers tailored for pulmonary administration. These nanocarriers offer benefits such as targeted deposition in specific areas of the tracheobronchial tree, controlled drug release, protection of active pharmaceutical ingredients (APIs) from lung clearance mechanisms, and cell-specific targeting. Research on nanomedicine for pulmonary delivery has progressed significantly, resulting in the development of several (nano)formulations, devices, and products in various stages of clinical development, with some already commercially available. Recent studies have focused on improving inhalation device testing, aerosol formulation development, and the application of in vitro, ex vivo, in vivo, and in silico models to better understand pulmonary drug deposition and disposition.

Conclusion

This review highlights the anatomical and physiological features of the lungs, recent advances in nanocarrier design and inhalation technologies. In addition, the applications in respiratory and systemic disease management have also been included. While significant progress has been made, challenges remain in optimizing pulmonary drug delivery systems, necessitating further research to address these complexities and enhance the therapeutic outcomes.

Background

The significant increase in infectious bacterial diseases over the past two decades presents a serious global health threat, compounded by the limited efficacy of current therapeutic options. This has created an urgent need to explore novel antibacterial compounds. Traditional preclinical animal models used to evaluate drug candidates are often costly and require lengthy testing periods. The previous studies have shown Drosophila melanogaster to be an effective model organism for antibacterial drug discovery. In this study, we evaluated the in vivo antibacterial effects of metformin and aspirin against Staphylococcus aureus using a Drosophila infection model.

Results

Our findings demonstrated that treatment with both metformin and aspirin significantly increased the survival of D. melanogaster infected with S. aureus. Additionally, both compounds inhibited bacterial growth in infected flies, as evidenced by reduced bacterial counts, indicating a direct antibacterial effect. Treatment also led to the downregulation of immune response-related genes, suggesting that the antibacterial activity occurred without immune system activation. Furthermore, metformin and aspirin reduced cell stress induced by bacterial infection, and these effects were validated in immunodeficient mutant flies, proving their efficacy independent of innate immune responses.

Conclusion

These findings highlight the potential for repurposing metformin and aspirin as antibacterial agents. Using a high-throughput, cost-effective, and efficient Drosophila model, this study provides strong evidence supporting the viability of these compounds as treatments against bacterial infections.

Background

Soy-based diets are commonly used not only by humans but also by laboratory and domesticated animals. Recently, there has been much argument around soybeans and their products, mostly due to their phytoestrogen (PE) content. Intestinal microflora digests soybean isoflavones to produce estrogenic compounds such as genistein, daidzein, and equol, which can bind with estrogen receptors (ERs). In recent years, the consumption of soybean-formulated diets has increased significantly. Our study is designed to evaluate the effects of soybean-formulated diets exposure from perinatal to puberty on the fertility of male mice.

Methods

Thirty pregnant dams are classified into three groups: the control group (CG);soy-free group is fed on a casein-based diet, while the second and third groups are fed on diets containing 20% and 30% soy in both low and high soy groups(LSG and HSG), respectively, from gestational day (GD) 12 till postnatal day (PND) 21 (weaning day). Male offspring are isolated and fed on the same diet groups from PND 21 to 56 (killing day).

Results

Male mice fed on soy-based diets showed a significant reduction in body and testes weights, as well as reproductive performance. Additionally, there was a decrease in sperm count, viability, and motility, while sperm abnormalities increased. Serum total testosterone levels and total antioxidant capacities (TAC) also decreased. Conversely, levels of follicular-stimulating hormone (FSH) and luteinizing hormone (LH) increased, along with sperm DNA fragmentation. The diameters of seminiferous tubules and the heights of the seminiferous epithelium were reduced. Furthermore, the soy-based diet affected testicular histology.

Conclusions

These observations indicate that soybean-based diets during perinatal and postnatal exposures negatively impact male fertility.

Background

Folate is essential for Deoxyribonucleic acid (DNA) synthesis, methylation and repair, with deficiencies linked to neural tube defects, Alzheimer’s, and cancer. Certain lactic acid bacteria (LAB), particularly in fermented dairy products, are natural folate producers. However, genetic insights into high-yielding strains remain limited. This study isolates indigenous lactic acid bacteria (LAB) and provides the first genetic mapping of folate biosynthesis in Streptococcus thermophilus (S. thermophilus).

Methods

Probiotic bacteria were isolated from locally sourced milk and yogurt samples and were subjected to morphological, biochemical, and molecular identification. The isolates were screened for folate production levels. Molecular studies and “in-silico” analysis were carried out to investigate the genetic basis of folate biosynthesis, particularly in S. thermophilus.

Results

Two folate-producing probiotic strains, Enterococcus faecium (E. faecium) and S. thermophilus, were isolated and characterized. Quantitative analysis revealed folate production levels of 2.2–8.3 µg/L and 156–162 µg/L, respectively, demonstrating significantly higher synthesis by S. thermophilus. In this strain, seven folate biosynthesis genes and one metabolism gene were identified and mapped. Five of the biosynthetic genes were found to be clustered: folC2 (encoding dihydrofolate synthase), folE (encoding GTP cyclohydrolase I), folP (encoding dihydropteroate synthase), folB (encoding dihydroneopterin aldolase, and folK (encoding 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase). The remaining genes were dispersed throughout the genome. A conserved Shine-Dalgarno sequence (AGGAG) was found 5 base-pair (bp) upstream of five genes.

Conclusion

This study elucidates the genetic basis of folate production in S. thermophilus, enabling future metabolic engineering for enhanced folate yields. The findings support strain selection for folate-enriched functional foods.

Background

Eimeria infection of poultry species is one of the famous parasitic diseases, Eimeria tenella is the most prevalent one in the field. This article aims to know the immune-haematological effect of E. tenella as a stress factor in birds vaccinated with Newcastle disease and IBD vaccine. For this study, fifty one-day-old broilers were used and divided into five groups: group A is control (non-vaccinated non-infected birds), group B was infected with E. tenella and vaccinated with Lasota vaccine, group C was infected with E. tenella parasite and vaccinated with IBD intermediate plus vaccine, group D was non-infected and vaccinated with Lasota vaccine, and group E was non-infected and vaccinated with IBD intermediate plus vaccine. Different parameters like oocyst count, body weight (BW), and vaccinal titer were estimated and in addition, erythrogram, leukogram, protein carbonyl (PC), superoxide dismutase (SOD), and interleukin 1β (IL1β) levels were also evaluated.

Results

The infected groups were characterized by a remarkable alteration in oocysts count and a noticeable reduction in BW, vaccinal titers, SOD, and IL1β. In addition, high PC, with marked anemia, leukocytopenia, and lymphocytosis were seen in infected groups. While, normal BW, increasable SOD, and IL1β levels along with, leukocytosis and lymphocytosis were prominent changes in vaccinated groups only.

Conclusion

The coccidian infection has adverse effects on healthy performance parameters including body weight, haematological, immune profiles, and ND and IBD vaccination.

Background

The rise of antimicrobial resistance among bacteria necessitates the exploration of alternative therapeutic strategies. One potential approach is combining antibiotics with vitamins to improve antimicrobial efficacy. This study investigates the synergistic effect of ceftazidime and vitamin C against Pseudomonas aeruginosa using Drosophila melanogaster larvae as an in vivo model.

Results

A series of microbiological, phenotypic, and molecular assays were conducted to evaluate the antibacterial effects of ceftazidime combined with vitamin C in the Drosophila model. Ceftazidime’s minimum inhibitory concentration (MIC) decreased from 12.5 to 6.25 µM when combined with vitamin C, according to the microdilution checkerboard assay. According to in vivo tests, D. melanogaster larvae treated with the antibiotic–vitamin C combination had a significantly higher survival rate (p < 0.05) than the infection control group. Colony-forming unit analysis on cetrimide agar medium showed no bacterial growth in the group treated with ceftazidime and vitamin C. Additionally, gene expression analysis demonstrated that ceftazidime treatment alone decreased Dpt gene expression through the IMD pathway, whereas the combination treatment elevated Dpt expression, reflecting the immunostimulant properties of vitamin C.

Conclusion

This study shows enhanced efficacy of ceftazidime when combined with vitamin C in the D. melanogaster larvae model. These findings parallel results from mammalian systems and support the use of Drosophila as a valuable pre-screening model for drug repurposing efforts aimed at combating antimicrobial resistance.

Background

In patients who are undergoing open cardiac surgery, thoracic paravertebral block (TPVB) is advantageous for pain management. Our objective was to compare this type of block with intravenous Fentanyl analgesia in those patients.

Methodology

This prospective, randomized study included 44 patients who underwent open-heart surgery through a median sternotomy. Participants were randomly divided into two equal groups (each with 22 subjects). Group I (Fentanyl group) (n = 22): received fentanyl infusion 2 µg/kg/h after placing the endotracheal tube and stopped at the end of surgery. Group II (TPVB group) (n = 22): Bilateral thoracic paravertebral catheters were inserted preoperative. Before induction, there was a maximum of 20 ml per side for each catheter, which received a bolus dose of 0.3 ml/kg 0.25% bupivacaine. Continuous infusion of 0.25% bupivacaine at a rate of 0.1 ml/kg/h was administered through each catheter following intubation. The infusion was subsequently discontinued at the conclusion of the procedure.

Results

Critical-Care Pain Observation Tool (CCPOT) was lower in patients of group II (TPVB group) than in patients of group I (fentanyl group); in group II at 8 h, 12 h, and 24 h postoperative were 2,3,3, respectively, whereas median CCPOT in group I at 8 h, 12 h, and 24 h postoperative were 3,4,4, respectively (p-value < 0.05). In comparison with group I, there was a substantial decrease in the intraoperative fentanyl requirements of group II (343.6 µg ± 44.1 and 926.8 µg ± 117.4) (p-value < 0.05). In comparison with group I (9 mg 2), the TPVB group’s postoperative opioid requirements were significantly lower (6.2 mg 2.3). P-value was less than 0.05.

Conclusion

Compared with IV fentanyl infusion, Bilateral continuous thoracic paravertebral block was determined to be more effective in the operative and postoperative analgesia of patients who underwent heart surgery via median sternotomy.

Background

Dehaasia pugerensis Koord. & Valeton is an endemic plant species classified as critically endangered (CR) in Jember, Java. It thrives in arid, rocky forest regions, making it a significant genetic resource for plant conservation initiatives. This study aimed to analyze the genetics of Dehaasia pugerensis through a molecular approach utilizing DNA (deoxyribonucleic acid) barcoding technique. This experiment utilized three accessions from three populations in Puger Jember, East Java: Igir Pletes (IP), Watu Susu (WS), and Undak Sebanen (US), along with Klatakan (KT). Notably, samples from the WS accession were excluded from internal transcribed spacer (ITS) primers due to poor sequencing results and were substituted with samples from the US accession. A single sample from each population of Dehaasia pugerensis underwent DNA sequencing utilizing DNA barcoding markers from three chloroplast genes: ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL), maturase K (matK), and the transfer RNA-histidine and the photosystem II protein D1 (trnH-psbA) intergenic spacer, as well as one nuclear ITS region.

Results

Sequence analysis demonstrated identical base composition in the plastid genes rbcL and matK, minor variation in trnH-psbA intergenic spacer, and significant variation in the nuclear ITS region. This demonstrates that the evolutionary rate of the chloroplast genome is lower than that of the nuclear genome. The chloroplast and nuclear genomes exhibit significant differences in evolutionary rates, influenced by various internal and external factors such as inheritance mode, mutation rate, and evolutionary pressures. Phylogenetic analysis indicated that the three accessions clustered together within the same group, as determined by chloroplast genes and ITS region. The three accessions exhibit a close relationship with Dehaasia hainanensis and Dehaasia incrassata, as indicated by the genetic distance observed on the phylogenetic tree.

Conclusions

DNA barcoding with rbcL, matK, trnH-psbA intergenic spacer, and ITS confirmed the identity of Dehaasia pugerensis and revealed key genetic diversity. Phylogenetic analysis grouped the three accessions (KT450, IP42, WS152) into a single clade, closely related to Dehaasia hainanensis and Dehaasia incrassata, indicating shared evolutionary traits. While rbcL and matK were genetically stable, trnH-psbA intergenic spacer and ITS showed notable variability, particularly in ITS, which revealed important genetic differences. These findings highlight the value of molecular data in shaping conservation strategies for Dehaasia pugerensis, such as propagation, reintroduction, and seed banking.

Background

Knee osteoarthritis (OA) is a debilitating condition that can severely limit an individual's mobility and quality of life. This study evaluated the efficacy of colchicine therapy in promoting cartilage healing in a rat model with monosodium iodoacetate (MIA)-induced knee OA. Histological and biochemical changes as well as semiquantitative radiographic characteristics were used to evaluate this.

Methods

An experimental knee OA model was induced by MIA in rats. Subsequently, 40 Wistar albino female rats were randomly divided into four groups, each consisting of 10 rats: a negative control group, an osteoarthritic control group, an osteoarthritic reference group treated with meloxicam®, and an osteoarthritic group administered an intraperitoneal injection of colchicine. Body weight and knee diameter measurements were taken weekly. Semiquantitative radiographic imaging and enzyme-linked immunosorbent assay analysis were performed on serum samples to assess the levels of inflammatory cytokine interleukin-1 beta (IL-1β) and the anti-inflammatory cytokine interleukin-10 (IL-10) prior to the conclusion of the trial. Histological examination was conducted using hematoxylin and eosin staining.

Results

Colchicine significantly reduced the osteoarthritic conditions after six weeks of supplementation. We observed decreased joint diameters in response to treatment in OA animals. Colchicine significantly decreased the IL-1β (p = 0.000) and increased the IL-10 (p = 0.000) in the serum of osteoarthritic rats in response to treatment in OA rats compared to the OA group with no treatment. Colchicine reduced the osteoarthritic rats' radiographic scores and enhanced the knee joint's histological structure.

Conclusion

The results indicate that colchicine could be beneficial in the treatment of rats with MIA-induced knee osteoarthritis, as it appears to postpone cartilage deterioration and reduce the activity of inflammatory mediators.

Irisin, a myokine produced by cleaving fibronectin type III domain-containing protein 5 (FNDC5), is a key regulator of metabolic processes and cardiovascular health. Its discovery in 2012 sparked significant interest due to its potential to impact fat and glucose metabolism, convert white fat to brown, and reduce inflammation—crucial in managing metabolic syndrome, obesity, and diabetes. Found in various tissues, including the brain, liver, heart, kidneys, and skeletal muscle, irisin has been linked to improved metabolic dysregulation and increased energy expenditure. Moreover, it has the potential to enhance endothelial function, reduce oxidative stress, and possibly regulate blood pressure, all contributing to improved cardiovascular health. This review explores the promising potential of irisin as a treatment for cardiovascular diseases (CVDs), metabolic syndrome, and related conditions. While more research is needed to fully understand its pathways, the future of irisin-based therapies in clinical settings looks promising.