Endophytic Penicillium oxalicum AUMC 14898 from Opuntia ficus-indica: A Novel Source of Tannic Acid Inhibiting Virulence and Quorum Sensing of Extensively Drug-Resistant Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a harmful pathogen that causes a variety of acute and chronic infections through quorum sensing (QS) mechanisms. The increasing resistance of this bacterium to numerous antibiotics has created a demand for new medications that specifically target QS. Endophytes can be the source of compounds with antibacterial properties. This research is the first to examine tannic acid (TA) produced by endophytic fungus as a potential biotherapeutic agent. A novel endophytic fungal isolate identified as Penicillium oxalicum was derived from the cladodes of Opuntia ficus-indica (L.). The species identification for this isolate was confirmed through sequencing of the internal transcribed spacer region. The metabolites from the culture of this isolate were extracted using ethyl acetate, then separated and characterized using chromatographic methods. This led to the acquisition of TA, a compound that shows strong anti-QS and excellent antibacterial effects against extensively drug-resistant P. aeruginosa strains. Furthermore, it was shown that treating P. aeruginosa with the obtained TA reduced the secretion of virulence factors controlled by QS in a dose-dependent manner, indicating that TA inhibited the QS characteristics of P. aeruginosa. Simultaneously, TA significantly inhibited the expression of genes associated with QS, including rhlR/I, lasR/I, and pqsR. In addition, in silico virtual molecular docking showed that TA could efficiently bind to QS receptor proteins. Our results showed that P. oxalicum could be a new source of TA for the treatment of infections caused by extensively drug-resistant P. aeruginosa.

Molecular and serological diagnosis of the circulating Trypanosoma evansi in Egyptian livestock with risk factors assessment.

This study aimed to characterize and determine the prevalence and the associated risk factors of trypanosomiasis in different Egyptian livestock from various governorates using molecular and serological techniques, adding to an assessment of some biochemical alterations in serum samples. A total 1019 blood samples were collected from nine governorates in the period from January 2020 to September 2021 from cattle (n = 752), buffaloes (n = 42), sheep (n = 65), goats (n = 60), donkeys (n = 54), and horses (n = 46). Molecular investigation followed by sequencing confirmed the presence of only Trypanosoma evansi (T. evansi) infection with a prevalence rate of 3.73 % (38/1019). Serologically, T. evansi was detected by indirect ELISA in 11 samples out of 519 negative PCR ones, with an overall prevalence 2.1 %. Furthermore, statistical difference was found between investigated governorates in both molecular and seroprevalence. Surprisingly, the risk of T. evansi infection was significantly (P < 0.05) higher in winter (9.83 %) than in autumn (1.4 %), while no infection was recorded in the spring and summer seasons. No significant difference regarding animal hosts, age, and sex as risk factors was recorded. Serum biochemical analysis showed a non-significant decrease of total proteins, albumin, A/G ratio, and HDL-cholesterol in cattle, equine, and goats with a non-significant increase in total globulins level. In sheep, a significant increase was determined in all tested parameters except a significant decrease in the level of albumin and A/G ratio. To the best of our knowledge, this is the first large-scale epidemiological study determining the endemicity of the neglected T. evansi infection in different animal species in multiple governorates of Egypt. It is recommended to use both molecular and serological techniques for efficient diagnosis of trypanosomiasis as a preliminary approach to control the disease.

Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer's disease.

Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer's disorder via preventing the aggregation of amyloid-beta-peptide-Aß(1-42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer's disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer's-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aß-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer's disease medication.

Molecular screening of piroplasms and Anaplasmataceae agents in Hyalomma dromedarii ticks from camels over different seasons in Egypt.

Piroplasmosis, a disease of domestic and wild animals, is caused by tick-borne protozoa of the genera Babesia and Theileria, while anaplasmosis is caused by tick-borne bacteria of genera Anaplasma. Hyalomma dromedarii is the most dominant tick species infesting camels in Egypt and act as a vector of piroplasms, Anaplasma, Rickettsia and Ehrlichia spp. The available information concerning the detection of these pathogens in H. dromedarii infesting camels is limited. The present study aimed to evaluate the status of these pathogens in H. dromedarii ticks over four seasons of a year, in addition to investigate the infections of piroplasms and Anaplasmataceae besides their genetic diversity starting from June 2021 till April 2022. A total of 275 semi-engorged females of H. dromedarii were collected from different slaughtered camels, Toukh city slaughterhouse then investigated by Polymerase Chain Reaction (PCR) to detect piroplasms (Babesia spp., Theileria spp.) and Anaplasmataceae DNA targeting 18 S rRNA and 16 S rRNA genes, respectively followed by sequencing and phylogenetic analyses. Overall, piroplasms were detected in 38 ticks (13.8%), Babesia spp. was detected in 35 ticks (12.7%), while Theileria spp. was detected in one tick (0.4%). Anaplasmataceae was detected in 57 ticks (20.7%). Mixed infections of piroplasms and Anaplasmataceae were detected in 13 ticks (5%). Single infection either with piroplasms or Anaplasmataceae was detected in 25 (9%) and 44 (16%) ticks, respectively. The highest monthly rate of piroplasms was in April (spring) and Anaplasmataceae was in July (summer). Sequence analysis revealed that Babesia bigemina, Wolbachia spp. and Anaplasma marginale are the most dominant species in the examined tick samples. To the best of our knowledge, this study confirms the presence of B. bigemina, Wolbachia spp. and A. marginale in H. dromedarii in Egypt by sequencing.

Deprescribing of Antihypertensive Medications and Cognitive Function in Nursing Home Residents.

Importance: Antihypertensive medication deprescribing is common among nursing home residents, yet its association with cognitive decline remains uncertain. Objective: To investigate the association of deprescribing antihypertensive medication with changes in cognitive function in nursing home residents. Design, Setting, and Participants: This cohort study using a target trial emulation approach included VA long-term care residents aged 65 years or older with stays of at least 12 weeks from 2006 to 2019. Residents who were not prescribed antihypertensive medication, with blood pressure greater than 160/90 mm Hg, or with heart failure were excluded. Eligible residents with stable medication use for 4 weeks were classified into deprescribing or stable user groups and followed for 2 years or until death or discharge for intention-to-treat (ITT) analysis. Participants switching treatment groups were censored in the per-protocol analysis. Cognitive function measurements during follow-up were analyzed using an ordinal generalized linear mixed model, adjusting for confounders with inverse probability of treatment weighting. Per-protocol analysis included inverse probability of censoring weighting. Data analyses were performed from May 1, 2023, and July 1, 2024. Exposures: Deprescribing was defined as a reduction in the total number of antihypertensive medications or a decrease in medication dosage by 30%, sustained for a minimum of 2 weeks. Main Outcomes and Measures: Cognitive Function Scale (CFS) was classified as cognitively intact (CFS = 1), mildly impaired (CFS = 2), moderately impaired (CFS = 3), and severely impaired (CFS = 4). Results: Of 45 183 long-term care residents, 12 644 residents (mean [SD] age 77.7 [8.3] years; 329 [2.6%] females and 12 315 [97.4%] males) and 12 053 residents (mean [SD] age 77.7 [8.3] years; 314 [2.6%] females and 11 739 [97.4%] males) met eligibility for ITT and per-protocol analyses, respectively. At the end of the follow-up, 12.0% of residents had a worsened CFS (higher score) and 7.7% had an improved CFS (lower score) with 10.8% of the deprescribing group and 12.1% of the stable user group showing a worsened CFS score. In the per-protocol analysis, the deprescribing group had a 12% reduction in the odds of progressing to a worse CFS category per 12-week period (odds ratio, 0.88; 95% CI, 0.78-0.99) compared to the stable user group. Among residents with dementia, deprescribing was associated with 16% reduced odds of cognitive decline (odds ratio, 0.84; 95% CI, 0.72-0.98). These patterns remained consistent in the ITT analysis. Conclusions and Relevance: This cohort study indicates that deprescribing is associated with less cognitive decline in nursing home residents, particularly those with dementia. More data are needed to understand the benefits and harms of antihypertensive deprescribing to inform patient-centered medication management in nursing homes.

I reflect, therefore I am!, Exploring the use of a Voluntary Online Reflective Journal as a learning tool among postgraduate dental students.

INTRODUCTION: Reflection is widely used in all aspects of teaching and learning in dental education and makes a fundamental part of all learning activities for dental students. However, reflective tasks are often used with a clear purpose; for example, in completing e-portfolios or dealing with critical incidences. This study explores the use of optional online journals that Postgraduate (PG) dental students were encouraged to use as part of their own development. AIM: To explore how PG dental students perceive the use of optional online journals. MATERIALS AND METHODS: Data were collected via an anonymous questionnaire that included a word pool, Likert-scale statements and free text comment sections. RESULTS: Overall, 31 students (93%) responded to the questionnaire with high focus on the usefulness of the journal, with 58% selecting 'connecting with tutors' and 41% selecting 'keeping track' of their own learning and progress. The word 'reflection' was selected by 87% of participants when describing the use of the journal. Some participants, 29%, considered the journal as 'added pressure', and 41% felt it was 'extra work' as the journal, although voluntary, presented an added task to complete. All students made at least one entry in the online journal. CONCLUSION: The use of an optional online journal can be a useful tool in establishing connection between dental students and their tutors. Some postgraduate dental students valued the benefits of reflective journal without it being linked to assessments. Some concerns were reported around the time constraints as well as the added work related to taking part in such activity.

Harnessing the power of Neobacillus niacini AUMC-B524 for silver oxide nanoparticle synthesis: optimization, characterization, and bioactivity exploration.

BACKGROUND: Biotechnology provides a cost-effective way to produce nanomaterials such as silver oxide nanoparticles (Ag2ONPs), which have emerged as versatile entities with diverse applications. This study investigated the ability of endophytic bacteria to biosynthesize Ag2ONPs. RESULTS: A novel endophytic bacterial strain, Neobacillus niacini AUMC-B524, was isolated from Lycium shawii Roem. & Schult leaves and used to synthesize Ag2ONPS extracellularly. Plackett-Burman design and response surface approach was carried out to optimize the biosynthesis of Ag2ONPs (Bio-Ag2ONPs). Comprehensive characterization techniques, including UV-vis spectral analysis, Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction, dynamic light scattering analysis, Raman microscopy, and energy dispersive X-ray analysis, confirmed the precise composition of the Ag2ONPS. Bio-Ag2ONPs were effective against multidrug-resistant wound pathogens, with minimum inhibitory concentrations (1-25 µg mL-1). Notably, Bio-Ag2ONPs demonstrated no cytotoxic effects on human skin fibroblasts (HSF) in vitro, while effectively suppressing the proliferation of human epidermoid skin carcinoma (A-431) cells, inducing apoptosis and modulating the key apoptotic genes including Bcl-2 associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), Caspase-3 (Cas-3), and guardian of the genome (P53). CONCLUSIONS: These findings highlight the therapeutic potential of Bio-Ag2ONPs synthesized by endophytic N. niacini AUMC-B524, underscoring their antibacterial efficacy, anticancer activity, and biocompatibility, paving the way for novel therapeutic strategies.

Opportunities and shortcomings of AI for spatial epidemiology and health disparities research on aging and the life course.

Established spatial and life course methods have helped epidemiologists and health and medical geographers study the impact of individual and area-level determinants on health disparities. While these methods are effective, the emergence of Geospatial Artificial Intelligence (GeoAI) offers new opportunities to leverage complex and multi-scalar data in spatial aging and life course research. The objective of this perspective is three-fold: (1) to review established methods in aging, life course, and spatial epidemiology research; (2) to highlight some of the opportunities offered by GeoAI for enhancing research on health disparities across life course and aging research; (3) to discuss the shortcomings of using GeoAI methods in aging and life course studies.

Effect of light-, chemical-, and dual-cured universal adhesives on the internal adaptation of resin composites to pulpal and gingival internal walls.

PURPOSE: To compare the internal adaptation of restorative systems bonded to mid-coronal and gingival dentin using light-cured, chemical-cured, and dual-cured adhesives, both immediately and after aging. METHODS: 60 molars were selected and received occluso-mesial preparations with dentin gingival margins. Restorations were performed using different restorative systems with light-cured, chemical-cured, and dual-cured adhesives. Internal adaptation was assessed by examining the percentage of continuous margin (%CM) at the pulpal and gingival dentin under a scanning electron microscope at x200 magnification. Half of the teeth were stored in sterile water for 24 hours, while the other half underwent 10,000 thermal cycles. Micro-morphological analysis was conducted on representative samples at x1,000 magnification. RESULTS: The restorative system with light-cured adhesive exhibited significantly lower %CM values at the gingival dentin, particularly after aging. Aging had a negative impact on the %CM values of the pulpal and gingival dentin in restorative systems with light-cured and dual-cured adhesives. Regional dentin variations influenced the %CM values, especially after aging, regardless of the restorative system used. The tested restorative system with chemical-cured adhesive is preferable for achieving improved internal adaptation when bonding to both mid-coronal and gingival dentin, compared to the other tested systems. CLINICAL SIGNIFICANCE: The study highlights the variations in adhesive performance between different regional dentin areas using the tested restorative systems.

Effects of residential socioeconomic polarization on high blood pressure among nursing home residents.

OBJECTIVE: Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home. METHODS: 41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders. RESULTS: We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain. CONCLUSIONS: We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.

Valorization of edible films based on chitosan/hydroxyethyl cellulose/olive leaf extract and TiO2-NPs for preserving sour cream.

Biodegradable edible films for sour cream packaging were developed based on chitosan (CS), hydroxyethyl cellulose (HEC), Olive leaf extract (OE), and titanium dioxide nanoparticles (TiO2-NPs). The prepared CS/HEC/TiO2-OE bionanocomposite films were evaluated for their antimicrobial and antioxidant activities as well as using FT-IR, mechanical, permeability, and contact angle. The effect of developed films on the lipid oxidation, microbiological load, and chemical properties of sour cream was investigated. The fabricated films had an antimicrobial impact against all tested strains. The film containing 8 % OE showed effective protection against fat oxidation, with a peroxide value of 3.21 meq O2/kg, a para-anisidine value 5.40, and free fatty acids of 0.82 mg KOH/kg. The films with OE 4 % and 8 % have a good effect on the microbiological load of sour cream for 90 days. These films did not influence the chemical composition of sour cream and therefore can be used in this sort of dairy product.

Biochemical analysis of Hyalomma dromedarii salivary glands and gut tissues using SR-FTIR micro-spectroscopy.

Ticks are obligatory voracious blood feeders infesting diverse vertebrate hosts, that have a crucial role in the transmission of diverse pathogens that threaten human and animal health. The continuous emergence of tick-borne diseases due to combined worldwide climatic changes, human activities, and acaricide-resistant tick strains, necessitates the development of novel ameliorative tick control strategies such as vaccines. The synchrotron-based Fourier transform infrared micro-spectroscopy (SR-FTIR) is a bioanalytical microprobe capable of exploring the molecular chemistry within microstructures at a cellular or subcellular level and is considered as a nondestructive analytical approach for biological specimens. In this study, SR-FTIR analysis was able to explore a qualitative and semi-quantitative biochemical composition of gut and salivary glands of Hyalomma dromedarii (H. dromedarii) tick detecting differences in the biochemical composition of both tissues. A notable observation regarding Amide I secondary structure protein profile was the higher ratio of aggregated strands in salivary gland and beta turns in gut tissues. Regarding the lipid profile, there was a higher intensity of lipid regions in gut tissue when compared to salivary glands. This detailed information on the biochemical compositions of tick tissues could assist in selecting vaccine and/or control candidates. Altogether, these findings confirmed SR-FTIR spectroscopy as a tool for detecting differences in the biochemical composition of H. dromedarii salivary glands and gut tissues. This approach could potentially be extended to the analysis of other ticks that are vectors of important diseases such as babesiosis and theileriosis.

Design, synthesis, and mechanistic insight of novel imidazolones as potential EGFR inhibitors and apoptosis inducers.

As regards to the structural analysis and optimization of diverse potential EGFR inhibitors, two series of imidazolyl-2-cyanoprop-2-enimidothioates and ethyl imidazolylthiomethylacrylates were designed and constructed as potential EGFR suppressors. The cytotoxic effect of the prepared derivatives was assessed toward hepatic, breast, and prostate cancerous cells (Hep-G2, MCF-7, and PC-3). Three derivatives 3d, 3e, and 3f presented potent antiproliferative activity and selectivity against the examined tumor cells showing IC50 values at low micromolar levels. Hence, successive biological assays were applied to determine the probable mechanism of action of the new compounds. They exhibited significant EGFR suppression with an IC50 range of 0.137-0.507 µM. The most effective EGFR inhibitor 3f arrested the MCF-7 cell cycle at the S phase by inducing the apoptotic pathway that was confirmed via increasing the expression of Caspases 8, 9, and Bax, which are associated with Bcl-2 decline. Additionally, molecular docking displayed a distinctive interaction between 3f and EGFR binding pocket. Overall, this work introduces some novel imidazolyl-2-cyanoprop-2-enimidothioates and ethyl imidazolylthiomethylacrylates as potential cytotoxic and EGFR inhibitors that deserve further research in tumor therapy.

Effect of different restorative systems and aging on marginal adaptation of resin composites to deep proximal margins.

OBJECTIVES: To evaluate and compare the marginal integrity of different restorative systems bonded to proximal gingival dentin, and determine the consistency level of the results obtained by two in vitro methods. MATERIALS AND METHODS: Thirty molars received occluso-mesial preparations with dentin/cementum gingival margins. They were divided into three groups and restored using different restorative systems with light-cured (Adhese Universal), self-cured (Palfique universal bond), and dual-cured (Futurabond U) adhesives. The restoration/gingival dentin interfaces were observed using scanning electron microscopy (SEM) and evaluated based on the World Dental Federation (FDI) criteria. After 10,000 thermal cycles, the marginal integrity was re-evaluated. Marginal integrity was evaluated by the percentage of continuous margin (% CM) at ×200 for SEM and as the frequency of each score within the FDI ranking. RESULTS: No significant differences were found between the restorative systems immediately, however, the system with the light-cured adhesive had the lowest marginal integrity after aging. All tested restorative systems were adversely affected by aging. A moderate inverse correlation was identified between evaluation techniques. CONCLUSION: The tested restorative systems utilizing self-cured and dual-cured adhesives may be preferable for achieving optimal marginal integrity when bonding to deep proximal margins, compared to the tested system with light-cured adhesive. CLINICAL SIGNIFICANCE: When performing deep margin elevation, it is important to consider the adhesive system being used.

Periodontal Evaluation of Subgingival Open Sandwich Restorations: 2-Year Results of a Randomized Double-Blind Trial.

This study aimed to evaluate the periodontal responses of subgingival proximal margins elevated using different restorative materials. A total of 120 proximal cavities with dentin/cementum gingival margins were elevated using one of four materials (resin-modified glass ionomer, glass hybrid, flowable bulk-fill resin composite, or bioactive ionic resin) and completed with the same overlaying resin composite. At 2 weeks (baseline), 6 months, 1 year, and 2 years postrestoration, periodontal parameters and the radiographic distance between the restoration margin and bone crest were evaluated. Appropriate statistical analyses were performed. The values of all periodontal parameters increased with time, although only the increases in Plaque Index and probing depth within each material group were statistically significant. There were no statistically significant differences in any of the periodontal parameters between the different materials within the same evaluation period, nor between different time points or material groups in the radiographic distances. Both glass ionomer-based and resin-based materials were periodontally safe as subgingival open sandwich restorations.

Clinical evaluation of subgingival open sandwich restorations: 3-year results of a randomized double-blind trial.

OBJECTIVES: To provide a 3-year follow-up of previously treated patients to assess and compare the periodontal responses and clinical performance of proximal subgingival open sandwich restorations. MATERIALS AND METHODS: Ninety-five adults participated in the study, with a combined total of 120 compound Class II cavities. These cavities had gingival margins located below the CEJ. Four different restorative materials were used to elevate the dentin/cementum gingival margins of the cavities: resin-modified glass ionomer, glass hybrid, flowable bulk-fill composite, or ion-releasing material, which were then completed with the same overlaying composite. Different periodontal and clinical evaluations, based on the criteria set by the World Dental Federation (FDI) criteria, were performed at different time intervals, including baseline, 6 months, 1, 2, and 3 years. RESULTS: The type of base material did not affect the periodontal evaluations. There were no statistically significant differences between different time intervals or base material groups in any of the evaluated FDI parameters. However, the ion-releasing material scored significantly worse in the radiographic evaluation than any of the other groups. CONCLUSIONS: All tested materials are suitable for proximal subgingival open sandwich restorations, as long as the restoration/tooth margin is at least 2-mm away from the bone crest. CLINICAL SIGNIFICANCE: Clinicians can confidently choose any of the tested materials for proximal subgingival open sandwich restorations, as they have shown good outcomes from both periodontal and clinical perspectives.

Dysregulated miRNA-375, IL-17, TGF-ß, and Microminerals Are Associated with Calpain-10 SNP 19 in Diabetic Patients: Correlation with Diabetic Nephropathy Stages.

Zinc (Zn) and copper (Cu) have been shown to have the potential to improve glucose metabolism through interactions with cytokines and signaling events with multiple genes. miRNA-375 and the Calpin-10 gene are potential genetic biomarkers for the early prediction of diabetic nephropathy (DN). 128 healthy controls and 129 type 2 diabetic (T2DM) participants were matched for age and sex. Three subgroups were identified from the T2DM group: 39 patients had microalbuminuria, 41 had macroalbuminuria, and 49 patients had renal problems. Circulating miR-375 expression levels were measured via qPCR. Calpain-10 SNP 19 (rs3842570) genotyping was assessed with allele-specific PCR in all the included participants. Spectrophotometry was used to measure the concentrations of serum copper, zinc, and magnesium, while ELISA was used to measure the levels of TGF-ß and IL-17. There was significant up-regulation in the expression of miR-375 and serum levels of TGF-ß, IL-17, Cu, and the Cu/Zn ratio, whereas, in contrast to the control group, the Zn and Mg levels were lower in the T2DM group. The DN groups had significantly lower miR-375, TGF-ß, IL-17, Mg, and Zn levels compared with the T2DM without nephropathy group. Furthermore, between TGF-ß, IL-17, and miRNA-375, there were notable correlations. Calpain-10 SNP 19 genotype 22 and allele 2 were linked to a higher incidence of T2DM and DN. Significant TGF-ß, Cu, Cu/Zn ratio, HbAc1, and creatinine levels, but insignificant miRNA-375 levels, were associated with genotype 22 of Calpain-10 SNP 19. interactions between the Calpain-10 SNP 19 genotype 22 and IL-17, TGF-ß, mineral levels, and miRNA-375 might contribute to the aetiology of DN and T2DM and may have clinical implications for diagnosis and management.

Mycosynthesis of silver nanoparticles from endophytic Aspergillus flavipes AUMC 15772: ovat-statistical optimization, characterization and biological activities.

BACKGROUND: Mycosynthesis of silver nanoparticles (SNPs) offers a safe, eco-friendly, and promising alternative technique for large-scale manufacturing. Our study might be the first report that uses mycelial filtrate of an endophytic fungus, Aspergillus flavipes, for SNPs production under optimal conditions as an antimicrobial agent against clinical multidrug-resistant (MDR) wound pathogens. RESULTS: In the present study, among four different endophytic fungi isolated from leaves of Lycium shawii, the only one isolate that has the ability to mycosynthesize SNPs has been identified for the first time as Aspergillus flavipes AUMC 15772 and deposited in Genebank under the accession number OP521771. One variable at a time (OVAT) and Plackett Burman design (PBD) were conducted for enhancing the production of mycosynthesized SNPs (Myco-SNPs) through optimization using five independent variables. The overall optimal variables for increasing the mycosynthesis of SNPs from mycelial filtrate of A. flavipes as a novel endophytic fungus were a silver nitrate concentration of 2 mM, a pH of 7.0, an incubation time of 5 days, and a mycelial filtrate concentration of 30% in dark conditions. UV-visible spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FT-IR), X-ray spectroscopy (XRD), Transmission electron microscopy (TEM), and Selected-Area Electron Diffraction (SAED) patterns were used to characterize Myco-SNPs, which showed the peak of absorbance at 420 nm, and FTIR showed the bands at 3426.44, 2923.30, 1681.85, 1552.64, and 1023.02 cm-1, respectively, which illustrated the presence of polyphenols, hydroxyl, alkene, nitro compounds, and aliphatic amines, respectively. The XRD pattern revealed the formation of Myco-SNPs with good crystal quality at 2θ = 34.23° and 38.18°. The TEM image and SAED pattern show the spherical crystalline shape of Myco-SNPs with an average size of 6.9232 nm. High antibacterial activity of Myco-SNPs was recorded against MDR wound pathogens as studied by minimum inhibitory concentrations ranging from 8 to 32 µg/mL, time kill kinetics, and post-agent effects. Also, in vitro cell tests indicated that Myco-SNPs support the cell viability of human skin fibroblast cells as a nontoxic compound. CONCLUSION: The obtained results revealed the successful production of Myco-SNPs using the mycelial filtrate of A. flavipes, which may be a promising nontoxic alternative candidate for combating MDR wound pathogens.